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Alain Bélanger - One of the best experts on this subject based on the ideXlab platform.

  • effect of interleukins on ugt2b15 and ugt2b17 steroid uridine diphosphate glucuronosyltransferase expression and activity in the LNCaP Cell Line
    Endocrinology, 1998
    Co-Authors: Eric Levesque, Chantal Guillemette, Martin Beaulieu, Alain Bélanger
    Abstract:

    Cytokines are known to modulate the level of both phase 1 and phase 2 drug-metabolizing enzymes in hepatocytes. Although the effects of cytokines on cytochrome P450 (CYP450) enzymes are well understood, there is limited knowledge on how cytokines may affect steroid UDP-glucuronosyltransferase (UGT) phase 2 enzyme activity and expression in different Cell types, including hepatocytes and steroid target Cells. LNCaP Cells, which is a human prostate cancer Cell Line, is a good model to study the effect of cytokines in steroid target Cells because it is known to express steroidogenic enzymes, including UGT2B15 and UGT2B17, which are widely expressed steroid UGT enzymes known to conjugate androgens. In this study, we examined the possible interaction among interleukin-1α (IL-1α), IL-4, IL-6, and steroid UGT enzymes (UGT2B15 and UGT2B17). Treatment of LNCaP Cells with IL-1α led to a dose-dependent inhibition of dihydrotestosterone (DHT) glucuronidation. IL-1α decreased both UGT activity and LNCaP Cell prolifera...

  • Regulation of steroid glucuronosyltransferase activities and transcripts by androgen in the human prostatic cancer LNCaP Cell Line
    Endocrinology, 1996
    Co-Authors: Chantal Guillemette, Alain Bélanger
    Abstract:

    Although much attention has been focused on the synthesis of dihydrotestosterone (DHT), the inactivation and elimination of active androgens can also be key points in regulating androgen levels in tissues such as the prostate. Recent data suggest that 5alpha-reduced C19 steroids can be converted to glucuronide derivatives in the human prostate, leading to complete inactivation of these steroids. These results are supported by the recent finding of at least two steroid uridine diphosphoglucuronosyltransferase (UGT) enzymes in the prostate as well as in the human prostatic cancer LNCaP Cell Line. To ascertain the role of UGTs in regulating active steroid levels, we investigated the modulation of UGT levels in response to steroid treatments in LNCaP Cells. Results demonstrate the down-regulation of UGT activities specific for 3-hydroxysteroids and 17-hydroxy-steroids after treatment with androgens and estrogens. Treating the Cells with DHT or R1881 for 7 days inhibited UGT activity by 60%; however, 80% of th...

  • expression of transcripts encoding steroid udp glucuronosyltransferases in human prostate hyperplastic tissue and the LNCaP Cell Line
    Molecular and Cellular Endocrinology, 1995
    Co-Authors: Guy Belanger, Chantal Guillemette, Martin Beaulieu, Bruno Marcotte, Eric Levesque, Alain Bélanger
    Abstract:

    Abstract The UDP-glucuronosyltransferase (EC 2.4.1.17) enzymes transform many lipophilic compounds to more water-soluble products via conjugation with glucuronic acid. This conversion is responsible for enhancing the excretion of endogenous aglycones such as steroids. To date, several distinct isoforms of steroid UDP-glucuronosyltransferases (UGTs) have been isolated in the human liver. Among these UGTs, UGT2B7 is specific for estriol and 3,4-catechol estrogens, UGT2B15 glucuronidates 17β-hydroxy-C19 steroids while UGT2B10 has as yet an undescribed activity. To further demonstrate the presence of UGTs in peripheral tissues we studied the expression of these enzymes in human prostate hyperplastic tissue and the LNCaP Cell Line. Metabolism studies using intact LNCaP Cells in culture indicate the presence of UGT activities involved in the glucuronidation of 3α-hydroxysteroids (androsterone) and 17β-hydroxysteroids (testosterone and dihydrotestosterone). Northern blot analysis of poly(A + ) RNA from LNCaP Cells and prostate using a UGT2B15 cDNA probe revealed two bands of 2.0 and 2.3 kb. In order to identify more specifically the mRNAs detected in Northern blot analysis we used RNase protection and RT-PCR assays. The relatively high expression of UGT2B10 and UGT2B15 in LNCaP Cells was confirmed by RNase protection and RT-PCR, although, these approaches did not allow detection of UGT2B7 transcripts. Our studies demonstrate the presence of two UGT activities and at least two types of UGT transcripts in both the human prostate and the LNCaP Cells.

Eric Levesque - One of the best experts on this subject based on the ideXlab platform.

  • effect of interleukins on ugt2b15 and ugt2b17 steroid uridine diphosphate glucuronosyltransferase expression and activity in the LNCaP Cell Line
    Endocrinology, 1998
    Co-Authors: Eric Levesque, Chantal Guillemette, Martin Beaulieu, Alain Bélanger
    Abstract:

    Cytokines are known to modulate the level of both phase 1 and phase 2 drug-metabolizing enzymes in hepatocytes. Although the effects of cytokines on cytochrome P450 (CYP450) enzymes are well understood, there is limited knowledge on how cytokines may affect steroid UDP-glucuronosyltransferase (UGT) phase 2 enzyme activity and expression in different Cell types, including hepatocytes and steroid target Cells. LNCaP Cells, which is a human prostate cancer Cell Line, is a good model to study the effect of cytokines in steroid target Cells because it is known to express steroidogenic enzymes, including UGT2B15 and UGT2B17, which are widely expressed steroid UGT enzymes known to conjugate androgens. In this study, we examined the possible interaction among interleukin-1α (IL-1α), IL-4, IL-6, and steroid UGT enzymes (UGT2B15 and UGT2B17). Treatment of LNCaP Cells with IL-1α led to a dose-dependent inhibition of dihydrotestosterone (DHT) glucuronidation. IL-1α decreased both UGT activity and LNCaP Cell prolifera...

  • expression of transcripts encoding steroid udp glucuronosyltransferases in human prostate hyperplastic tissue and the LNCaP Cell Line
    Molecular and Cellular Endocrinology, 1995
    Co-Authors: Guy Belanger, Chantal Guillemette, Martin Beaulieu, Bruno Marcotte, Eric Levesque, Alain Bélanger
    Abstract:

    Abstract The UDP-glucuronosyltransferase (EC 2.4.1.17) enzymes transform many lipophilic compounds to more water-soluble products via conjugation with glucuronic acid. This conversion is responsible for enhancing the excretion of endogenous aglycones such as steroids. To date, several distinct isoforms of steroid UDP-glucuronosyltransferases (UGTs) have been isolated in the human liver. Among these UGTs, UGT2B7 is specific for estriol and 3,4-catechol estrogens, UGT2B15 glucuronidates 17β-hydroxy-C19 steroids while UGT2B10 has as yet an undescribed activity. To further demonstrate the presence of UGTs in peripheral tissues we studied the expression of these enzymes in human prostate hyperplastic tissue and the LNCaP Cell Line. Metabolism studies using intact LNCaP Cells in culture indicate the presence of UGT activities involved in the glucuronidation of 3α-hydroxysteroids (androsterone) and 17β-hydroxysteroids (testosterone and dihydrotestosterone). Northern blot analysis of poly(A + ) RNA from LNCaP Cells and prostate using a UGT2B15 cDNA probe revealed two bands of 2.0 and 2.3 kb. In order to identify more specifically the mRNAs detected in Northern blot analysis we used RNase protection and RT-PCR assays. The relatively high expression of UGT2B10 and UGT2B15 in LNCaP Cells was confirmed by RNase protection and RT-PCR, although, these approaches did not allow detection of UGT2B7 transcripts. Our studies demonstrate the presence of two UGT activities and at least two types of UGT transcripts in both the human prostate and the LNCaP Cells.

Carlo M Croce - One of the best experts on this subject based on the ideXlab platform.

  • the t 6 16 p21 q22 chromosome translocation in the LNCaP prostate carcinoma Cell Line results in a tpc hpr fusion gene
    Cancer Research, 1996
    Co-Authors: Maria Luisa Veronese, Florencia Bullrich, Massimo Negrini, Carlo M Croce
    Abstract:

    Abstract Very little is known about the molecular and genetic mechanisms involved in prostate cancer. Previous studies have shown frequent loss of heterozygosity (40%) at chromosomal regions 8p, 10q, and 16q, suggesting the presence of tumor suppressor genes in these regions. The LNCaP Cell Line, established from a metastatic lesion of human prostatic adenocarcinoma, carries a t(6;16)(p21;q22) translocation. To determine whether this translocation involved genes important in the process of malignant transformation, we cloned and sequenced the t(6;16) breakpoint of this Cell Line. Sequence analysis showed that the breakpoint is within the haptoglobin gene cluster on chromosome 16, and that, on chromosome 6, the break occurs within a novel gene, tpc , similar to the prokaryotic S10 ribosomal protein gene. The translocation results in the production of a fusion transcript, tpc/hpr .

  • The t(6;16)(p21;q22) chromosome translocation in the LNCaP prostate carcinoma Cell Line results in a tpc/hpr fusion gene.
    Cancer Research, 1996
    Co-Authors: Maria Luisa Veronese, Florencia Bullrich, Massimo Negrini, Carlo M Croce
    Abstract:

    Abstract Very little is known about the molecular and genetic mechanisms involved in prostate cancer. Previous studies have shown frequent loss of heterozygosity (40%) at chromosomal regions 8p, 10q, and 16q, suggesting the presence of tumor suppressor genes in these regions. The LNCaP Cell Line, established from a metastatic lesion of human prostatic adenocarcinoma, carries a t(6;16)(p21;q22) translocation. To determine whether this translocation involved genes important in the process of malignant transformation, we cloned and sequenced the t(6;16) breakpoint of this Cell Line. Sequence analysis showed that the breakpoint is within the haptoglobin gene cluster on chromosome 16, and that, on chromosome 6, the break occurs within a novel gene, tpc , similar to the prokaryotic S10 ribosomal protein gene. The translocation results in the production of a fusion transcript, tpc/hpr .

Chantal Guillemette - One of the best experts on this subject based on the ideXlab platform.

  • effect of interleukins on ugt2b15 and ugt2b17 steroid uridine diphosphate glucuronosyltransferase expression and activity in the LNCaP Cell Line
    Endocrinology, 1998
    Co-Authors: Eric Levesque, Chantal Guillemette, Martin Beaulieu, Alain Bélanger
    Abstract:

    Cytokines are known to modulate the level of both phase 1 and phase 2 drug-metabolizing enzymes in hepatocytes. Although the effects of cytokines on cytochrome P450 (CYP450) enzymes are well understood, there is limited knowledge on how cytokines may affect steroid UDP-glucuronosyltransferase (UGT) phase 2 enzyme activity and expression in different Cell types, including hepatocytes and steroid target Cells. LNCaP Cells, which is a human prostate cancer Cell Line, is a good model to study the effect of cytokines in steroid target Cells because it is known to express steroidogenic enzymes, including UGT2B15 and UGT2B17, which are widely expressed steroid UGT enzymes known to conjugate androgens. In this study, we examined the possible interaction among interleukin-1α (IL-1α), IL-4, IL-6, and steroid UGT enzymes (UGT2B15 and UGT2B17). Treatment of LNCaP Cells with IL-1α led to a dose-dependent inhibition of dihydrotestosterone (DHT) glucuronidation. IL-1α decreased both UGT activity and LNCaP Cell prolifera...

  • Regulation of steroid glucuronosyltransferase activities and transcripts by androgen in the human prostatic cancer LNCaP Cell Line
    Endocrinology, 1996
    Co-Authors: Chantal Guillemette, Alain Bélanger
    Abstract:

    Although much attention has been focused on the synthesis of dihydrotestosterone (DHT), the inactivation and elimination of active androgens can also be key points in regulating androgen levels in tissues such as the prostate. Recent data suggest that 5alpha-reduced C19 steroids can be converted to glucuronide derivatives in the human prostate, leading to complete inactivation of these steroids. These results are supported by the recent finding of at least two steroid uridine diphosphoglucuronosyltransferase (UGT) enzymes in the prostate as well as in the human prostatic cancer LNCaP Cell Line. To ascertain the role of UGTs in regulating active steroid levels, we investigated the modulation of UGT levels in response to steroid treatments in LNCaP Cells. Results demonstrate the down-regulation of UGT activities specific for 3-hydroxysteroids and 17-hydroxy-steroids after treatment with androgens and estrogens. Treating the Cells with DHT or R1881 for 7 days inhibited UGT activity by 60%; however, 80% of th...

  • expression of transcripts encoding steroid udp glucuronosyltransferases in human prostate hyperplastic tissue and the LNCaP Cell Line
    Molecular and Cellular Endocrinology, 1995
    Co-Authors: Guy Belanger, Chantal Guillemette, Martin Beaulieu, Bruno Marcotte, Eric Levesque, Alain Bélanger
    Abstract:

    Abstract The UDP-glucuronosyltransferase (EC 2.4.1.17) enzymes transform many lipophilic compounds to more water-soluble products via conjugation with glucuronic acid. This conversion is responsible for enhancing the excretion of endogenous aglycones such as steroids. To date, several distinct isoforms of steroid UDP-glucuronosyltransferases (UGTs) have been isolated in the human liver. Among these UGTs, UGT2B7 is specific for estriol and 3,4-catechol estrogens, UGT2B15 glucuronidates 17β-hydroxy-C19 steroids while UGT2B10 has as yet an undescribed activity. To further demonstrate the presence of UGTs in peripheral tissues we studied the expression of these enzymes in human prostate hyperplastic tissue and the LNCaP Cell Line. Metabolism studies using intact LNCaP Cells in culture indicate the presence of UGT activities involved in the glucuronidation of 3α-hydroxysteroids (androsterone) and 17β-hydroxysteroids (testosterone and dihydrotestosterone). Northern blot analysis of poly(A + ) RNA from LNCaP Cells and prostate using a UGT2B15 cDNA probe revealed two bands of 2.0 and 2.3 kb. In order to identify more specifically the mRNAs detected in Northern blot analysis we used RNase protection and RT-PCR assays. The relatively high expression of UGT2B10 and UGT2B15 in LNCaP Cells was confirmed by RNase protection and RT-PCR, although, these approaches did not allow detection of UGT2B7 transcripts. Our studies demonstrate the presence of two UGT activities and at least two types of UGT transcripts in both the human prostate and the LNCaP Cells.

Martin Beaulieu - One of the best experts on this subject based on the ideXlab platform.

  • effect of interleukins on ugt2b15 and ugt2b17 steroid uridine diphosphate glucuronosyltransferase expression and activity in the LNCaP Cell Line
    Endocrinology, 1998
    Co-Authors: Eric Levesque, Chantal Guillemette, Martin Beaulieu, Alain Bélanger
    Abstract:

    Cytokines are known to modulate the level of both phase 1 and phase 2 drug-metabolizing enzymes in hepatocytes. Although the effects of cytokines on cytochrome P450 (CYP450) enzymes are well understood, there is limited knowledge on how cytokines may affect steroid UDP-glucuronosyltransferase (UGT) phase 2 enzyme activity and expression in different Cell types, including hepatocytes and steroid target Cells. LNCaP Cells, which is a human prostate cancer Cell Line, is a good model to study the effect of cytokines in steroid target Cells because it is known to express steroidogenic enzymes, including UGT2B15 and UGT2B17, which are widely expressed steroid UGT enzymes known to conjugate androgens. In this study, we examined the possible interaction among interleukin-1α (IL-1α), IL-4, IL-6, and steroid UGT enzymes (UGT2B15 and UGT2B17). Treatment of LNCaP Cells with IL-1α led to a dose-dependent inhibition of dihydrotestosterone (DHT) glucuronidation. IL-1α decreased both UGT activity and LNCaP Cell prolifera...

  • expression of transcripts encoding steroid udp glucuronosyltransferases in human prostate hyperplastic tissue and the LNCaP Cell Line
    Molecular and Cellular Endocrinology, 1995
    Co-Authors: Guy Belanger, Chantal Guillemette, Martin Beaulieu, Bruno Marcotte, Eric Levesque, Alain Bélanger
    Abstract:

    Abstract The UDP-glucuronosyltransferase (EC 2.4.1.17) enzymes transform many lipophilic compounds to more water-soluble products via conjugation with glucuronic acid. This conversion is responsible for enhancing the excretion of endogenous aglycones such as steroids. To date, several distinct isoforms of steroid UDP-glucuronosyltransferases (UGTs) have been isolated in the human liver. Among these UGTs, UGT2B7 is specific for estriol and 3,4-catechol estrogens, UGT2B15 glucuronidates 17β-hydroxy-C19 steroids while UGT2B10 has as yet an undescribed activity. To further demonstrate the presence of UGTs in peripheral tissues we studied the expression of these enzymes in human prostate hyperplastic tissue and the LNCaP Cell Line. Metabolism studies using intact LNCaP Cells in culture indicate the presence of UGT activities involved in the glucuronidation of 3α-hydroxysteroids (androsterone) and 17β-hydroxysteroids (testosterone and dihydrotestosterone). Northern blot analysis of poly(A + ) RNA from LNCaP Cells and prostate using a UGT2B15 cDNA probe revealed two bands of 2.0 and 2.3 kb. In order to identify more specifically the mRNAs detected in Northern blot analysis we used RNase protection and RT-PCR assays. The relatively high expression of UGT2B10 and UGT2B15 in LNCaP Cells was confirmed by RNase protection and RT-PCR, although, these approaches did not allow detection of UGT2B7 transcripts. Our studies demonstrate the presence of two UGT activities and at least two types of UGT transcripts in both the human prostate and the LNCaP Cells.