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Elias Castanas - One of the best experts on this subject based on the ideXlab platform.

  • the opioid agonist ethylketocyclazocine reverts the rapid non genomic effects of membrane Testosterone Receptors in the human prostate lncap cell line
    2004
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Vassiliaismini Alexaki, Christos Stournaras, Anastassia Hatzoglou, Elias Castanas
    Abstract:

    Abstract Neuropeptides influence cancer cell replication and growth. Opioid peptides, and opiergic neurons are found in the prostate gland, and they are proposed to exert a role in tumor regulation, influencing cancer cell growth, as opioid agonists inhibit cell growth in several systems, including the human prostate cancer cell line LNCaP. In the same cell line, the existence of membrane Testosterone Receptors was recently reported, which increase, in a non-genomic manner, the secretion of PSA, and modify actin cytoskeleton dynamics, through the signaling cascade FAK→PI-3 kinase→Cdc42/Rac1. In the present work, we present data supporting that the general opioid agonist Ethylketocyclazocine (EKC) decreases Testosterone-BSA (a non-internalizable Testosterone analog) induced PSA secretion. Furthermore, we report that this opioid affects this non-genomic Testosterone action, by modifying the distribution of the actin cytoskeleton in the cells, disrupting the above signaling cascade. In addition, after long (>24 h) incubation, opioids decrease the number of membrane Testosterone Receptors, and reverse their effect on the signaling molecules. In conclusion, our results provide some new insights of a possible action of opioids in prostate cancer control by interfering with the action and the expression of membrane Testosterone Receptors and signaling.

  • a rapid nongenomic signaling pathway regulates the actin reorganization induced by activation of membrane Testosterone Receptors
    2003
    Co-Authors: Evangelia A Papakonstanti, Elias Castanas, Marilena Kampa, Christos Stournaras
    Abstract:

    The human prostate cancer cell line LNCaP bears functional membrane Testosterone Receptors, which modify the actin cytoskeleton and increase the secretion of prostate-specific antigen (PSA) within minutes. Membrane steroid Receptors are, indeed, a newly identified element of steroid action that is different from the classical intracellular sites. In the present work, using a nonpermeable analog of Testosterone (Testosterone-BSA), we investigated the signaling pathway that is triggered by the membrane Testosterone Receptors' activation and leads to actin cytoskeleton reorganization. We report that exposure of cells to Testosterone-BSA resulted in phosphorylation of focal adhesion kinase (FAK), the association of FAK with the phosphatidylinositol-3 (PI-3) kinase, and the subsequent activation of the latter as well as the activation of the small guanosine triphosphatases Cdc42/Rac1. Pretreatment of cells with the specific PI-3 kinase inhibitor wortmannin abolished both the activation of the small guanosine triphosphatases and the alterations of actin cytoskeleton, whereas it did not affect the phosphorylation of FAK. These findings indicate that PI-3 kinase is activated downstream of FAK and upstream of Cdc42/Rac1, which subsequently regulate the actin organization. Moreover, wortmannin diminished the secretion of PSA, implying that the signaling events described above are responsible for the Testosterone-BSA-induced PSA secretion. Our results are discussed under the prism of a possible implication of these membrane Receptors in prostate cancer chemotherapy.

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors that increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    Recent findings have shown that, in addition to the genomic action of steroids, through intracellular Receptors, short-time effects could be mediated through binding to membrane sites. In the present study of prostate cancer LNCaP cells, we report that dihydroTestosterone and the non-internalizable analog Testosterone-BSA increase rapidly the release of prostate-specific antigen (PSA) in the culture medium. Membrane Testosterone binding sites were identified through ligand binding on membrane preparations, flow cytometry, and confocal laser microscopy of the non-internalizable fluorescent analog Testosterone-BSA-FITC, on whole cells. Binding on these sites is time- and concentration-dependent and specific for Testosterone, presenting a KD of 10.9 nM and a number of 144 sites/mg protein (approximately 13000 sites/cell). Membrane sites differ immunologically for intracellular androgen Receptors. The secretion of PSA after membrane Testosterone receptor stimulation was inhibited after pretreatment with the actin cytoskeleton disrupting agent cytochalasin B. In addition, membrane Testosterone binding modifies the intracellular dynamic equilibrium of monomeric to filamentous actin and remodels profoundly the actin cytoskeleton organization. These results are discussed in the context of a possible involvement of these sites in cancer chemotherapy.

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors that increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    SPECIFIC AIMDifferent steroids enter the cell and exert their action after binding to intracellular proteins, the respective cognitive hormone Receptors, sharing characteristics of nuclear transcription factors. In recent years, however, some reports have indicated that these hormones may also act through membrane binding sites by a mechanism not involving nuclear effects. In the present work, we report the identification of a membrane receptor for Testosterone in the human hormone receptor-positive cell line LNCaP. We show that this binding site is different from the classical androgen receptor and that its activation results, within minutes, in actin polymerization, redistribution of actin cytoskeleton, and an increase of PSA secretion in the culture medium.PRINCIPAL FINDINGS1. Testosterone induces PSA secretion by LNCaP cells through membrane sites, different from classical androgen ReceptorsIn LNCaP cells, Testosterone and its biologically active metabolite dihydroTestosterone (DHT) increased, in a do...

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors which increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    SPECIFIC AIMDifferent steroids enter the cell and exert their action after binding to intracellular proteins, the respective cognitive hormone Receptors, sharing characteristics of nuclear transcription factors. In recent years, however, some reports have indicated that these hormones may also act through membrane binding sites by a mechanism not involving nuclear effects. In the present work, we report the identification of a membrane receptor for Testosterone in the human hormone receptor-positive cell line LNCaP. We show that this binding site is different from the classical androgen receptor and that its activation results, within minutes, in actin polymerization, redistribution of actin cytoskeleton, and an increase of PSA secretion in the culture medium.PRINCIPAL FINDINGS1. Testosterone induces PSA secretion by LNCaP cells through membrane sites, different from classical androgen ReceptorsIn LNCaP cells, Testosterone and its biologically active metabolite dihydroTestosterone (DHT) increased, in a do...

Marilena Kampa - One of the best experts on this subject based on the ideXlab platform.

  • the opioid agonist ethylketocyclazocine reverts the rapid non genomic effects of membrane Testosterone Receptors in the human prostate lncap cell line
    2004
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Vassiliaismini Alexaki, Christos Stournaras, Anastassia Hatzoglou, Elias Castanas
    Abstract:

    Abstract Neuropeptides influence cancer cell replication and growth. Opioid peptides, and opiergic neurons are found in the prostate gland, and they are proposed to exert a role in tumor regulation, influencing cancer cell growth, as opioid agonists inhibit cell growth in several systems, including the human prostate cancer cell line LNCaP. In the same cell line, the existence of membrane Testosterone Receptors was recently reported, which increase, in a non-genomic manner, the secretion of PSA, and modify actin cytoskeleton dynamics, through the signaling cascade FAK→PI-3 kinase→Cdc42/Rac1. In the present work, we present data supporting that the general opioid agonist Ethylketocyclazocine (EKC) decreases Testosterone-BSA (a non-internalizable Testosterone analog) induced PSA secretion. Furthermore, we report that this opioid affects this non-genomic Testosterone action, by modifying the distribution of the actin cytoskeleton in the cells, disrupting the above signaling cascade. In addition, after long (>24 h) incubation, opioids decrease the number of membrane Testosterone Receptors, and reverse their effect on the signaling molecules. In conclusion, our results provide some new insights of a possible action of opioids in prostate cancer control by interfering with the action and the expression of membrane Testosterone Receptors and signaling.

  • a rapid nongenomic signaling pathway regulates the actin reorganization induced by activation of membrane Testosterone Receptors
    2003
    Co-Authors: Evangelia A Papakonstanti, Elias Castanas, Marilena Kampa, Christos Stournaras
    Abstract:

    The human prostate cancer cell line LNCaP bears functional membrane Testosterone Receptors, which modify the actin cytoskeleton and increase the secretion of prostate-specific antigen (PSA) within minutes. Membrane steroid Receptors are, indeed, a newly identified element of steroid action that is different from the classical intracellular sites. In the present work, using a nonpermeable analog of Testosterone (Testosterone-BSA), we investigated the signaling pathway that is triggered by the membrane Testosterone Receptors' activation and leads to actin cytoskeleton reorganization. We report that exposure of cells to Testosterone-BSA resulted in phosphorylation of focal adhesion kinase (FAK), the association of FAK with the phosphatidylinositol-3 (PI-3) kinase, and the subsequent activation of the latter as well as the activation of the small guanosine triphosphatases Cdc42/Rac1. Pretreatment of cells with the specific PI-3 kinase inhibitor wortmannin abolished both the activation of the small guanosine triphosphatases and the alterations of actin cytoskeleton, whereas it did not affect the phosphorylation of FAK. These findings indicate that PI-3 kinase is activated downstream of FAK and upstream of Cdc42/Rac1, which subsequently regulate the actin organization. Moreover, wortmannin diminished the secretion of PSA, implying that the signaling events described above are responsible for the Testosterone-BSA-induced PSA secretion. Our results are discussed under the prism of a possible implication of these membrane Receptors in prostate cancer chemotherapy.

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors that increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    Recent findings have shown that, in addition to the genomic action of steroids, through intracellular Receptors, short-time effects could be mediated through binding to membrane sites. In the present study of prostate cancer LNCaP cells, we report that dihydroTestosterone and the non-internalizable analog Testosterone-BSA increase rapidly the release of prostate-specific antigen (PSA) in the culture medium. Membrane Testosterone binding sites were identified through ligand binding on membrane preparations, flow cytometry, and confocal laser microscopy of the non-internalizable fluorescent analog Testosterone-BSA-FITC, on whole cells. Binding on these sites is time- and concentration-dependent and specific for Testosterone, presenting a KD of 10.9 nM and a number of 144 sites/mg protein (approximately 13000 sites/cell). Membrane sites differ immunologically for intracellular androgen Receptors. The secretion of PSA after membrane Testosterone receptor stimulation was inhibited after pretreatment with the actin cytoskeleton disrupting agent cytochalasin B. In addition, membrane Testosterone binding modifies the intracellular dynamic equilibrium of monomeric to filamentous actin and remodels profoundly the actin cytoskeleton organization. These results are discussed in the context of a possible involvement of these sites in cancer chemotherapy.

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors that increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    SPECIFIC AIMDifferent steroids enter the cell and exert their action after binding to intracellular proteins, the respective cognitive hormone Receptors, sharing characteristics of nuclear transcription factors. In recent years, however, some reports have indicated that these hormones may also act through membrane binding sites by a mechanism not involving nuclear effects. In the present work, we report the identification of a membrane receptor for Testosterone in the human hormone receptor-positive cell line LNCaP. We show that this binding site is different from the classical androgen receptor and that its activation results, within minutes, in actin polymerization, redistribution of actin cytoskeleton, and an increase of PSA secretion in the culture medium.PRINCIPAL FINDINGS1. Testosterone induces PSA secretion by LNCaP cells through membrane sites, different from classical androgen ReceptorsIn LNCaP cells, Testosterone and its biologically active metabolite dihydroTestosterone (DHT) increased, in a do...

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors which increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    SPECIFIC AIMDifferent steroids enter the cell and exert their action after binding to intracellular proteins, the respective cognitive hormone Receptors, sharing characteristics of nuclear transcription factors. In recent years, however, some reports have indicated that these hormones may also act through membrane binding sites by a mechanism not involving nuclear effects. In the present work, we report the identification of a membrane receptor for Testosterone in the human hormone receptor-positive cell line LNCaP. We show that this binding site is different from the classical androgen receptor and that its activation results, within minutes, in actin polymerization, redistribution of actin cytoskeleton, and an increase of PSA secretion in the culture medium.PRINCIPAL FINDINGS1. Testosterone induces PSA secretion by LNCaP cells through membrane sites, different from classical androgen ReceptorsIn LNCaP cells, Testosterone and its biologically active metabolite dihydroTestosterone (DHT) increased, in a do...

Christos Stournaras - One of the best experts on this subject based on the ideXlab platform.

  • the opioid agonist ethylketocyclazocine reverts the rapid non genomic effects of membrane Testosterone Receptors in the human prostate lncap cell line
    2004
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Vassiliaismini Alexaki, Christos Stournaras, Anastassia Hatzoglou, Elias Castanas
    Abstract:

    Abstract Neuropeptides influence cancer cell replication and growth. Opioid peptides, and opiergic neurons are found in the prostate gland, and they are proposed to exert a role in tumor regulation, influencing cancer cell growth, as opioid agonists inhibit cell growth in several systems, including the human prostate cancer cell line LNCaP. In the same cell line, the existence of membrane Testosterone Receptors was recently reported, which increase, in a non-genomic manner, the secretion of PSA, and modify actin cytoskeleton dynamics, through the signaling cascade FAK→PI-3 kinase→Cdc42/Rac1. In the present work, we present data supporting that the general opioid agonist Ethylketocyclazocine (EKC) decreases Testosterone-BSA (a non-internalizable Testosterone analog) induced PSA secretion. Furthermore, we report that this opioid affects this non-genomic Testosterone action, by modifying the distribution of the actin cytoskeleton in the cells, disrupting the above signaling cascade. In addition, after long (>24 h) incubation, opioids decrease the number of membrane Testosterone Receptors, and reverse their effect on the signaling molecules. In conclusion, our results provide some new insights of a possible action of opioids in prostate cancer control by interfering with the action and the expression of membrane Testosterone Receptors and signaling.

  • a rapid nongenomic signaling pathway regulates the actin reorganization induced by activation of membrane Testosterone Receptors
    2003
    Co-Authors: Evangelia A Papakonstanti, Elias Castanas, Marilena Kampa, Christos Stournaras
    Abstract:

    The human prostate cancer cell line LNCaP bears functional membrane Testosterone Receptors, which modify the actin cytoskeleton and increase the secretion of prostate-specific antigen (PSA) within minutes. Membrane steroid Receptors are, indeed, a newly identified element of steroid action that is different from the classical intracellular sites. In the present work, using a nonpermeable analog of Testosterone (Testosterone-BSA), we investigated the signaling pathway that is triggered by the membrane Testosterone Receptors' activation and leads to actin cytoskeleton reorganization. We report that exposure of cells to Testosterone-BSA resulted in phosphorylation of focal adhesion kinase (FAK), the association of FAK with the phosphatidylinositol-3 (PI-3) kinase, and the subsequent activation of the latter as well as the activation of the small guanosine triphosphatases Cdc42/Rac1. Pretreatment of cells with the specific PI-3 kinase inhibitor wortmannin abolished both the activation of the small guanosine triphosphatases and the alterations of actin cytoskeleton, whereas it did not affect the phosphorylation of FAK. These findings indicate that PI-3 kinase is activated downstream of FAK and upstream of Cdc42/Rac1, which subsequently regulate the actin organization. Moreover, wortmannin diminished the secretion of PSA, implying that the signaling events described above are responsible for the Testosterone-BSA-induced PSA secretion. Our results are discussed under the prism of a possible implication of these membrane Receptors in prostate cancer chemotherapy.

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors that increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    Recent findings have shown that, in addition to the genomic action of steroids, through intracellular Receptors, short-time effects could be mediated through binding to membrane sites. In the present study of prostate cancer LNCaP cells, we report that dihydroTestosterone and the non-internalizable analog Testosterone-BSA increase rapidly the release of prostate-specific antigen (PSA) in the culture medium. Membrane Testosterone binding sites were identified through ligand binding on membrane preparations, flow cytometry, and confocal laser microscopy of the non-internalizable fluorescent analog Testosterone-BSA-FITC, on whole cells. Binding on these sites is time- and concentration-dependent and specific for Testosterone, presenting a KD of 10.9 nM and a number of 144 sites/mg protein (approximately 13000 sites/cell). Membrane sites differ immunologically for intracellular androgen Receptors. The secretion of PSA after membrane Testosterone receptor stimulation was inhibited after pretreatment with the actin cytoskeleton disrupting agent cytochalasin B. In addition, membrane Testosterone binding modifies the intracellular dynamic equilibrium of monomeric to filamentous actin and remodels profoundly the actin cytoskeleton organization. These results are discussed in the context of a possible involvement of these sites in cancer chemotherapy.

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors that increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    SPECIFIC AIMDifferent steroids enter the cell and exert their action after binding to intracellular proteins, the respective cognitive hormone Receptors, sharing characteristics of nuclear transcription factors. In recent years, however, some reports have indicated that these hormones may also act through membrane binding sites by a mechanism not involving nuclear effects. In the present work, we report the identification of a membrane receptor for Testosterone in the human hormone receptor-positive cell line LNCaP. We show that this binding site is different from the classical androgen receptor and that its activation results, within minutes, in actin polymerization, redistribution of actin cytoskeleton, and an increase of PSA secretion in the culture medium.PRINCIPAL FINDINGS1. Testosterone induces PSA secretion by LNCaP cells through membrane sites, different from classical androgen ReceptorsIn LNCaP cells, Testosterone and its biologically active metabolite dihydroTestosterone (DHT) increased, in a do...

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors which increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    SPECIFIC AIMDifferent steroids enter the cell and exert their action after binding to intracellular proteins, the respective cognitive hormone Receptors, sharing characteristics of nuclear transcription factors. In recent years, however, some reports have indicated that these hormones may also act through membrane binding sites by a mechanism not involving nuclear effects. In the present work, we report the identification of a membrane receptor for Testosterone in the human hormone receptor-positive cell line LNCaP. We show that this binding site is different from the classical androgen receptor and that its activation results, within minutes, in actin polymerization, redistribution of actin cytoskeleton, and an increase of PSA secretion in the culture medium.PRINCIPAL FINDINGS1. Testosterone induces PSA secretion by LNCaP cells through membrane sites, different from classical androgen ReceptorsIn LNCaP cells, Testosterone and its biologically active metabolite dihydroTestosterone (DHT) increased, in a do...

Evangelia A Papakonstanti - One of the best experts on this subject based on the ideXlab platform.

  • the opioid agonist ethylketocyclazocine reverts the rapid non genomic effects of membrane Testosterone Receptors in the human prostate lncap cell line
    2004
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Vassiliaismini Alexaki, Christos Stournaras, Anastassia Hatzoglou, Elias Castanas
    Abstract:

    Abstract Neuropeptides influence cancer cell replication and growth. Opioid peptides, and opiergic neurons are found in the prostate gland, and they are proposed to exert a role in tumor regulation, influencing cancer cell growth, as opioid agonists inhibit cell growth in several systems, including the human prostate cancer cell line LNCaP. In the same cell line, the existence of membrane Testosterone Receptors was recently reported, which increase, in a non-genomic manner, the secretion of PSA, and modify actin cytoskeleton dynamics, through the signaling cascade FAK→PI-3 kinase→Cdc42/Rac1. In the present work, we present data supporting that the general opioid agonist Ethylketocyclazocine (EKC) decreases Testosterone-BSA (a non-internalizable Testosterone analog) induced PSA secretion. Furthermore, we report that this opioid affects this non-genomic Testosterone action, by modifying the distribution of the actin cytoskeleton in the cells, disrupting the above signaling cascade. In addition, after long (>24 h) incubation, opioids decrease the number of membrane Testosterone Receptors, and reverse their effect on the signaling molecules. In conclusion, our results provide some new insights of a possible action of opioids in prostate cancer control by interfering with the action and the expression of membrane Testosterone Receptors and signaling.

  • a rapid nongenomic signaling pathway regulates the actin reorganization induced by activation of membrane Testosterone Receptors
    2003
    Co-Authors: Evangelia A Papakonstanti, Elias Castanas, Marilena Kampa, Christos Stournaras
    Abstract:

    The human prostate cancer cell line LNCaP bears functional membrane Testosterone Receptors, which modify the actin cytoskeleton and increase the secretion of prostate-specific antigen (PSA) within minutes. Membrane steroid Receptors are, indeed, a newly identified element of steroid action that is different from the classical intracellular sites. In the present work, using a nonpermeable analog of Testosterone (Testosterone-BSA), we investigated the signaling pathway that is triggered by the membrane Testosterone Receptors' activation and leads to actin cytoskeleton reorganization. We report that exposure of cells to Testosterone-BSA resulted in phosphorylation of focal adhesion kinase (FAK), the association of FAK with the phosphatidylinositol-3 (PI-3) kinase, and the subsequent activation of the latter as well as the activation of the small guanosine triphosphatases Cdc42/Rac1. Pretreatment of cells with the specific PI-3 kinase inhibitor wortmannin abolished both the activation of the small guanosine triphosphatases and the alterations of actin cytoskeleton, whereas it did not affect the phosphorylation of FAK. These findings indicate that PI-3 kinase is activated downstream of FAK and upstream of Cdc42/Rac1, which subsequently regulate the actin organization. Moreover, wortmannin diminished the secretion of PSA, implying that the signaling events described above are responsible for the Testosterone-BSA-induced PSA secretion. Our results are discussed under the prism of a possible implication of these membrane Receptors in prostate cancer chemotherapy.

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors that increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    Recent findings have shown that, in addition to the genomic action of steroids, through intracellular Receptors, short-time effects could be mediated through binding to membrane sites. In the present study of prostate cancer LNCaP cells, we report that dihydroTestosterone and the non-internalizable analog Testosterone-BSA increase rapidly the release of prostate-specific antigen (PSA) in the culture medium. Membrane Testosterone binding sites were identified through ligand binding on membrane preparations, flow cytometry, and confocal laser microscopy of the non-internalizable fluorescent analog Testosterone-BSA-FITC, on whole cells. Binding on these sites is time- and concentration-dependent and specific for Testosterone, presenting a KD of 10.9 nM and a number of 144 sites/mg protein (approximately 13000 sites/cell). Membrane sites differ immunologically for intracellular androgen Receptors. The secretion of PSA after membrane Testosterone receptor stimulation was inhibited after pretreatment with the actin cytoskeleton disrupting agent cytochalasin B. In addition, membrane Testosterone binding modifies the intracellular dynamic equilibrium of monomeric to filamentous actin and remodels profoundly the actin cytoskeleton organization. These results are discussed in the context of a possible involvement of these sites in cancer chemotherapy.

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors that increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    SPECIFIC AIMDifferent steroids enter the cell and exert their action after binding to intracellular proteins, the respective cognitive hormone Receptors, sharing characteristics of nuclear transcription factors. In recent years, however, some reports have indicated that these hormones may also act through membrane binding sites by a mechanism not involving nuclear effects. In the present work, we report the identification of a membrane receptor for Testosterone in the human hormone receptor-positive cell line LNCaP. We show that this binding site is different from the classical androgen receptor and that its activation results, within minutes, in actin polymerization, redistribution of actin cytoskeleton, and an increase of PSA secretion in the culture medium.PRINCIPAL FINDINGS1. Testosterone induces PSA secretion by LNCaP cells through membrane sites, different from classical androgen ReceptorsIn LNCaP cells, Testosterone and its biologically active metabolite dihydroTestosterone (DHT) increased, in a do...

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors which increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    SPECIFIC AIMDifferent steroids enter the cell and exert their action after binding to intracellular proteins, the respective cognitive hormone Receptors, sharing characteristics of nuclear transcription factors. In recent years, however, some reports have indicated that these hormones may also act through membrane binding sites by a mechanism not involving nuclear effects. In the present work, we report the identification of a membrane receptor for Testosterone in the human hormone receptor-positive cell line LNCaP. We show that this binding site is different from the classical androgen receptor and that its activation results, within minutes, in actin polymerization, redistribution of actin cytoskeleton, and an increase of PSA secretion in the culture medium.PRINCIPAL FINDINGS1. Testosterone induces PSA secretion by LNCaP cells through membrane sites, different from classical androgen ReceptorsIn LNCaP cells, Testosterone and its biologically active metabolite dihydroTestosterone (DHT) increased, in a do...

Anastassia Hatzoglou - One of the best experts on this subject based on the ideXlab platform.

  • the opioid agonist ethylketocyclazocine reverts the rapid non genomic effects of membrane Testosterone Receptors in the human prostate lncap cell line
    2004
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Vassiliaismini Alexaki, Christos Stournaras, Anastassia Hatzoglou, Elias Castanas
    Abstract:

    Abstract Neuropeptides influence cancer cell replication and growth. Opioid peptides, and opiergic neurons are found in the prostate gland, and they are proposed to exert a role in tumor regulation, influencing cancer cell growth, as opioid agonists inhibit cell growth in several systems, including the human prostate cancer cell line LNCaP. In the same cell line, the existence of membrane Testosterone Receptors was recently reported, which increase, in a non-genomic manner, the secretion of PSA, and modify actin cytoskeleton dynamics, through the signaling cascade FAK→PI-3 kinase→Cdc42/Rac1. In the present work, we present data supporting that the general opioid agonist Ethylketocyclazocine (EKC) decreases Testosterone-BSA (a non-internalizable Testosterone analog) induced PSA secretion. Furthermore, we report that this opioid affects this non-genomic Testosterone action, by modifying the distribution of the actin cytoskeleton in the cells, disrupting the above signaling cascade. In addition, after long (>24 h) incubation, opioids decrease the number of membrane Testosterone Receptors, and reverse their effect on the signaling molecules. In conclusion, our results provide some new insights of a possible action of opioids in prostate cancer control by interfering with the action and the expression of membrane Testosterone Receptors and signaling.

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors that increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    Recent findings have shown that, in addition to the genomic action of steroids, through intracellular Receptors, short-time effects could be mediated through binding to membrane sites. In the present study of prostate cancer LNCaP cells, we report that dihydroTestosterone and the non-internalizable analog Testosterone-BSA increase rapidly the release of prostate-specific antigen (PSA) in the culture medium. Membrane Testosterone binding sites were identified through ligand binding on membrane preparations, flow cytometry, and confocal laser microscopy of the non-internalizable fluorescent analog Testosterone-BSA-FITC, on whole cells. Binding on these sites is time- and concentration-dependent and specific for Testosterone, presenting a KD of 10.9 nM and a number of 144 sites/mg protein (approximately 13000 sites/cell). Membrane sites differ immunologically for intracellular androgen Receptors. The secretion of PSA after membrane Testosterone receptor stimulation was inhibited after pretreatment with the actin cytoskeleton disrupting agent cytochalasin B. In addition, membrane Testosterone binding modifies the intracellular dynamic equilibrium of monomeric to filamentous actin and remodels profoundly the actin cytoskeleton organization. These results are discussed in the context of a possible involvement of these sites in cancer chemotherapy.

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors that increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    SPECIFIC AIMDifferent steroids enter the cell and exert their action after binding to intracellular proteins, the respective cognitive hormone Receptors, sharing characteristics of nuclear transcription factors. In recent years, however, some reports have indicated that these hormones may also act through membrane binding sites by a mechanism not involving nuclear effects. In the present work, we report the identification of a membrane receptor for Testosterone in the human hormone receptor-positive cell line LNCaP. We show that this binding site is different from the classical androgen receptor and that its activation results, within minutes, in actin polymerization, redistribution of actin cytoskeleton, and an increase of PSA secretion in the culture medium.PRINCIPAL FINDINGS1. Testosterone induces PSA secretion by LNCaP cells through membrane sites, different from classical androgen ReceptorsIn LNCaP cells, Testosterone and its biologically active metabolite dihydroTestosterone (DHT) increased, in a do...

  • the human prostate cancer cell line lncap bears functional membrane Testosterone Receptors which increase psa secretion and modify actin cytoskeleton
    2002
    Co-Authors: Marilena Kampa, Evangelia A Papakonstanti, Christos Stournaras, Anastassia Hatzoglou, Efstathios N Stathopoulos, Elias Castanas
    Abstract:

    SPECIFIC AIMDifferent steroids enter the cell and exert their action after binding to intracellular proteins, the respective cognitive hormone Receptors, sharing characteristics of nuclear transcription factors. In recent years, however, some reports have indicated that these hormones may also act through membrane binding sites by a mechanism not involving nuclear effects. In the present work, we report the identification of a membrane receptor for Testosterone in the human hormone receptor-positive cell line LNCaP. We show that this binding site is different from the classical androgen receptor and that its activation results, within minutes, in actin polymerization, redistribution of actin cytoskeleton, and an increase of PSA secretion in the culture medium.PRINCIPAL FINDINGS1. Testosterone induces PSA secretion by LNCaP cells through membrane sites, different from classical androgen ReceptorsIn LNCaP cells, Testosterone and its biologically active metabolite dihydroTestosterone (DHT) increased, in a do...