The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform
Alexander Yu Nikitin - One of the best experts on this subject based on the ideXlab platform.
-
prostate cancer associated with p53 and rb deficiency arises from the stem progenitor cell enriched proximal region of Prostatic Ducts
Cancer Research, 2007Co-Authors: Zongxiang Zhou, Andrea Fleskennikitin, Alexander Yu NikitinAbstract:Recently, we have shown that prostate epithelium-specific deficiency for p53 and Rb tumor suppressors leads to metastatic cancer, exhibiting features of both luminal and neuroendocrine differentiation. Using stage-by-stage evaluation of carcinogenesis in this model, we report that all malignant neoplasms arise from the proximal region of the Prostatic Ducts, the compartment highly enriched for Prostatic stem/progenitor cells. In close similarity to reported properties of Prostatic stem cells, the cells of the earliest neoplastic lesions express stem cell marker stem cell antigen 1 and are not sensitive to androgen withdrawal. Like a subset of normal cells located in the proximal region of Prostatic Ducts, the early neoplastic cells coexpress luminal epithelium markers cytokeratin 8, androgen receptor, and neuroendocrine markers synaptophysin and chromogranin A. Inactivation of p53 and Rb also takes place in the lineage-committed transit-amplifying and/or differentiated cells of the distal region of the Prostatic Ducts. However, the resulting Prostatic intraepithelial neoplasms never progress to carcinoma by the time of mouse death. Interestingly, in an ectopic transplantation assay, early mutant cells derived from either region of the Prostatic Ducts are capable of forming neoplasms within 3 months. These findings indicate that p53 and Rb are critically important for the regulation of the Prostatic stem cell compartment, the transformation in which may lead to particularly aggressive cancers in the context of microenvironment.
-
Prostate cancer associated with p53 and Rb deficiency arises from the stem/progenitor cell-enriched proximal region of Prostatic Ducts.
Cancer Research, 2007Co-Authors: Zongxiang Zhou, Andrea Flesken-nikitin, Alexander Yu NikitinAbstract:Recently, we have shown that prostate epithelium-specific deficiency for p53 and Rb tumor suppressors leads to metastatic cancer, exhibiting features of both luminal and neuroendocrine differentiation. Using stage-by-stage evaluation of carcinogenesis in this model, we report that all malignant neoplasms arise from the proximal region of the Prostatic Ducts, the compartment highly enriched for Prostatic stem/progenitor cells. In close similarity to reported properties of Prostatic stem cells, the cells of the earliest neoplastic lesions express stem cell marker stem cell antigen 1 and are not sensitive to androgen withdrawal. Like a subset of normal cells located in the proximal region of Prostatic Ducts, the early neoplastic cells coexpress luminal epithelium markers cytokeratin 8, androgen receptor, and neuroendocrine markers synaptophysin and chromogranin A. Inactivation of p53 and Rb also takes place in the lineage-committed transit-amplifying and/or differentiated cells of the distal region of the Prostatic Ducts. However, the resulting Prostatic intraepithelial neoplasms never progress to carcinoma by the time of mouse death. Interestingly, in an ectopic transplantation assay, early mutant cells derived from either region of the Prostatic Ducts are capable of forming neoplasms within 3 months. These findings indicate that p53 and Rb are critically important for the regulation of the Prostatic stem cell compartment, the transformation in which may lead to particularly aggressive cancers in the context of microenvironment.
Sarah N Salm - One of the best experts on this subject based on the ideXlab platform.
-
tgf β maintains dormancy of Prostatic stem cells in the proximal region of Ducts
Journal of Cell Biology, 2005Co-Authors: Patricia E Burger, Sandra Coetzee, Sarah N Salm, David Moscatelli, Ken Goto, Lynette E WilsonAbstract:We have previously shown that Prostatic stem cells are located in the proximal region of mouse Prostatic Ducts. Here, we show that this region responds differently to transforming growth factor (TGF)-β than the distal ductal region and that under physiological conditions androgens and TGF-β are crucial overall regulators of Prostatic tissue homeostasis. This conclusion is supported by the observations showing that high levels of TGF-β signaling are present in the quiescent proximal region of Ducts in an androgen-replete animal and that cells in this region overexpress Bcl-2, which protects them from apoptosis. Moreover, androgen ablation reverses the proximal-distal TGF-β signaling gradient, leading to an increase in TGF-β signaling in the unprotected distal region (low Bcl-2 expression). This reversal of TGF-β–mediated signaling accompanies apoptosis of cells in the distal region and gland involution after androgen withdrawal. A physiological TGF-β signaling gradient (high proximally and low distally) and its functional correlates are restored after androgen replenishment. In addition to highlighting the regulatory role of androgens and TGF-β, these findings may have important implications for the deregulation of the stem cell compartment in the etiology of proliferative Prostatic diseases.
-
sca 1 expression identifies stem cells in the proximal region of Prostatic Ducts with high capacity to reconstitute Prostatic tissue
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Patricia E Burger, Xiaozhong Xiong, Sandra Coetzee, Sarah N Salm, David Moscatelli, Ken Goto, Lynette E WilsonAbstract:We previously showed that Prostatic stem cells are concentrated in the proximal regions of Prostatic Ducts. We now report that these stem cells can be purified from isolated proximal duct regions by virtue of their high expression of the cell surface protein stem cell antigen 1 (Sca-1). In an in vivo prostate reconstitution assay, the purified Sca-1-expressing cell population isolated from the proximal region of Ducts was more effective in generating Prostatic tissue than a comparable population of Sca-1-depleted cells (203.0 ± 83.1 mg vs. 11.9 ± 9.2 mg) or a population of Sca-1-expressing cells isolated from the remaining regions of Ducts (transit-amplifying cells) (31.9 ± 24.1 mg). Almost all of the proliferative capacity of the proximal duct Sca-1-expressing cell population resides within the fraction of cells that express high levels of Sca-1 (top one-third), with the proximal region of Prostatic Ducts containing 7.2-fold more Sca-1high cells than the remaining regions. More than 60% of the high-expressing cells coexpress α6 integrin and the antiapoptotic factor Bcl-2, markers that are also characteristic of stem cells of other origins. Further stratification of the phenotype of the stem cells may enable the development of rational therapies for treating prostate cancer and benign Prostatic hyperplasia.
-
Proximal location of mouse prostate epithelial stem cells: a model of Prostatic homeostasis
Journal of Cell Biology, 2002Co-Authors: Akira Tsujimura, Sandra Coetzee, Sarah N Salm, David Moscatelli, Yasuhiro Koikawa, Tetsuya Takao, Ellen Shapiro, Herbert Lepor, E. Lynette WilsonAbstract:Stem cells are believed to regulate normal Prostatic homeostasis and to play a role in the etiology of prostate cancer and benign Prostatic hyperplasia. We show here that the proximal region of mouse Prostatic Ducts is enriched in a subpopulation of epithelial cells that exhibit three important attributes of epithelial stem cells: they are slow cycling, possess a high in vitro proliferative potential, and can reconstitute highly branched glandular ductal structures in collagen gels. We propose a model of Prostatic homeostasis in which mouse Prostatic epithelial stem cells are concentrated in the proximal region of Prostatic Ducts while the transit-amplifying cells occupy the distal region of the Ducts. This model can account for many biological differences between cells of the proximal and distal regions, and has implications for Prostatic disease formation.
Lynette E Wilson - One of the best experts on this subject based on the ideXlab platform.
-
tgf β maintains dormancy of Prostatic stem cells in the proximal region of Ducts
Journal of Cell Biology, 2005Co-Authors: Patricia E Burger, Sandra Coetzee, Sarah N Salm, David Moscatelli, Ken Goto, Lynette E WilsonAbstract:We have previously shown that Prostatic stem cells are located in the proximal region of mouse Prostatic Ducts. Here, we show that this region responds differently to transforming growth factor (TGF)-β than the distal ductal region and that under physiological conditions androgens and TGF-β are crucial overall regulators of Prostatic tissue homeostasis. This conclusion is supported by the observations showing that high levels of TGF-β signaling are present in the quiescent proximal region of Ducts in an androgen-replete animal and that cells in this region overexpress Bcl-2, which protects them from apoptosis. Moreover, androgen ablation reverses the proximal-distal TGF-β signaling gradient, leading to an increase in TGF-β signaling in the unprotected distal region (low Bcl-2 expression). This reversal of TGF-β–mediated signaling accompanies apoptosis of cells in the distal region and gland involution after androgen withdrawal. A physiological TGF-β signaling gradient (high proximally and low distally) and its functional correlates are restored after androgen replenishment. In addition to highlighting the regulatory role of androgens and TGF-β, these findings may have important implications for the deregulation of the stem cell compartment in the etiology of proliferative Prostatic diseases.
-
sca 1 expression identifies stem cells in the proximal region of Prostatic Ducts with high capacity to reconstitute Prostatic tissue
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Patricia E Burger, Xiaozhong Xiong, Sandra Coetzee, Sarah N Salm, David Moscatelli, Ken Goto, Lynette E WilsonAbstract:We previously showed that Prostatic stem cells are concentrated in the proximal regions of Prostatic Ducts. We now report that these stem cells can be purified from isolated proximal duct regions by virtue of their high expression of the cell surface protein stem cell antigen 1 (Sca-1). In an in vivo prostate reconstitution assay, the purified Sca-1-expressing cell population isolated from the proximal region of Ducts was more effective in generating Prostatic tissue than a comparable population of Sca-1-depleted cells (203.0 ± 83.1 mg vs. 11.9 ± 9.2 mg) or a population of Sca-1-expressing cells isolated from the remaining regions of Ducts (transit-amplifying cells) (31.9 ± 24.1 mg). Almost all of the proliferative capacity of the proximal duct Sca-1-expressing cell population resides within the fraction of cells that express high levels of Sca-1 (top one-third), with the proximal region of Prostatic Ducts containing 7.2-fold more Sca-1high cells than the remaining regions. More than 60% of the high-expressing cells coexpress α6 integrin and the antiapoptotic factor Bcl-2, markers that are also characteristic of stem cells of other origins. Further stratification of the phenotype of the stem cells may enable the development of rational therapies for treating prostate cancer and benign Prostatic hyperplasia.
Ken Goto - One of the best experts on this subject based on the ideXlab platform.
-
tgf β maintains dormancy of Prostatic stem cells in the proximal region of Ducts
Journal of Cell Biology, 2005Co-Authors: Patricia E Burger, Sandra Coetzee, Sarah N Salm, David Moscatelli, Ken Goto, Lynette E WilsonAbstract:We have previously shown that Prostatic stem cells are located in the proximal region of mouse Prostatic Ducts. Here, we show that this region responds differently to transforming growth factor (TGF)-β than the distal ductal region and that under physiological conditions androgens and TGF-β are crucial overall regulators of Prostatic tissue homeostasis. This conclusion is supported by the observations showing that high levels of TGF-β signaling are present in the quiescent proximal region of Ducts in an androgen-replete animal and that cells in this region overexpress Bcl-2, which protects them from apoptosis. Moreover, androgen ablation reverses the proximal-distal TGF-β signaling gradient, leading to an increase in TGF-β signaling in the unprotected distal region (low Bcl-2 expression). This reversal of TGF-β–mediated signaling accompanies apoptosis of cells in the distal region and gland involution after androgen withdrawal. A physiological TGF-β signaling gradient (high proximally and low distally) and its functional correlates are restored after androgen replenishment. In addition to highlighting the regulatory role of androgens and TGF-β, these findings may have important implications for the deregulation of the stem cell compartment in the etiology of proliferative Prostatic diseases.
-
sca 1 expression identifies stem cells in the proximal region of Prostatic Ducts with high capacity to reconstitute Prostatic tissue
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Patricia E Burger, Xiaozhong Xiong, Sandra Coetzee, Sarah N Salm, David Moscatelli, Ken Goto, Lynette E WilsonAbstract:We previously showed that Prostatic stem cells are concentrated in the proximal regions of Prostatic Ducts. We now report that these stem cells can be purified from isolated proximal duct regions by virtue of their high expression of the cell surface protein stem cell antigen 1 (Sca-1). In an in vivo prostate reconstitution assay, the purified Sca-1-expressing cell population isolated from the proximal region of Ducts was more effective in generating Prostatic tissue than a comparable population of Sca-1-depleted cells (203.0 ± 83.1 mg vs. 11.9 ± 9.2 mg) or a population of Sca-1-expressing cells isolated from the remaining regions of Ducts (transit-amplifying cells) (31.9 ± 24.1 mg). Almost all of the proliferative capacity of the proximal duct Sca-1-expressing cell population resides within the fraction of cells that express high levels of Sca-1 (top one-third), with the proximal region of Prostatic Ducts containing 7.2-fold more Sca-1high cells than the remaining regions. More than 60% of the high-expressing cells coexpress α6 integrin and the antiapoptotic factor Bcl-2, markers that are also characteristic of stem cells of other origins. Further stratification of the phenotype of the stem cells may enable the development of rational therapies for treating prostate cancer and benign Prostatic hyperplasia.
Zongxiang Zhou - One of the best experts on this subject based on the ideXlab platform.
-
prostate cancer associated with p53 and rb deficiency arises from the stem progenitor cell enriched proximal region of Prostatic Ducts
Cancer Research, 2007Co-Authors: Zongxiang Zhou, Andrea Fleskennikitin, Alexander Yu NikitinAbstract:Recently, we have shown that prostate epithelium-specific deficiency for p53 and Rb tumor suppressors leads to metastatic cancer, exhibiting features of both luminal and neuroendocrine differentiation. Using stage-by-stage evaluation of carcinogenesis in this model, we report that all malignant neoplasms arise from the proximal region of the Prostatic Ducts, the compartment highly enriched for Prostatic stem/progenitor cells. In close similarity to reported properties of Prostatic stem cells, the cells of the earliest neoplastic lesions express stem cell marker stem cell antigen 1 and are not sensitive to androgen withdrawal. Like a subset of normal cells located in the proximal region of Prostatic Ducts, the early neoplastic cells coexpress luminal epithelium markers cytokeratin 8, androgen receptor, and neuroendocrine markers synaptophysin and chromogranin A. Inactivation of p53 and Rb also takes place in the lineage-committed transit-amplifying and/or differentiated cells of the distal region of the Prostatic Ducts. However, the resulting Prostatic intraepithelial neoplasms never progress to carcinoma by the time of mouse death. Interestingly, in an ectopic transplantation assay, early mutant cells derived from either region of the Prostatic Ducts are capable of forming neoplasms within 3 months. These findings indicate that p53 and Rb are critically important for the regulation of the Prostatic stem cell compartment, the transformation in which may lead to particularly aggressive cancers in the context of microenvironment.
-
Prostate cancer associated with p53 and Rb deficiency arises from the stem/progenitor cell-enriched proximal region of Prostatic Ducts.
Cancer Research, 2007Co-Authors: Zongxiang Zhou, Andrea Flesken-nikitin, Alexander Yu NikitinAbstract:Recently, we have shown that prostate epithelium-specific deficiency for p53 and Rb tumor suppressors leads to metastatic cancer, exhibiting features of both luminal and neuroendocrine differentiation. Using stage-by-stage evaluation of carcinogenesis in this model, we report that all malignant neoplasms arise from the proximal region of the Prostatic Ducts, the compartment highly enriched for Prostatic stem/progenitor cells. In close similarity to reported properties of Prostatic stem cells, the cells of the earliest neoplastic lesions express stem cell marker stem cell antigen 1 and are not sensitive to androgen withdrawal. Like a subset of normal cells located in the proximal region of Prostatic Ducts, the early neoplastic cells coexpress luminal epithelium markers cytokeratin 8, androgen receptor, and neuroendocrine markers synaptophysin and chromogranin A. Inactivation of p53 and Rb also takes place in the lineage-committed transit-amplifying and/or differentiated cells of the distal region of the Prostatic Ducts. However, the resulting Prostatic intraepithelial neoplasms never progress to carcinoma by the time of mouse death. Interestingly, in an ectopic transplantation assay, early mutant cells derived from either region of the Prostatic Ducts are capable of forming neoplasms within 3 months. These findings indicate that p53 and Rb are critically important for the regulation of the Prostatic stem cell compartment, the transformation in which may lead to particularly aggressive cancers in the context of microenvironment.
