Accumulating progenitor cells in the luminal epithelial cell layer are candidate tumor initiating cells in a Pten knockout mouse prostate cancer model
The PSA-Cre;Pten-loxP/loxP mouse prostate cancer model displays clearly defined stages of hyperplasia and cancer. Here, the initial stages of hyperplasia development are studied. Immunohistochemical staining showed that accumulated pAkt+ hyperplastic cells overexpress luminal epithelial cell marker...
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| creator | Korsten, Hanneke Ziel-van der Made, Angelique Ma, Xiaoqian van der Kwast, Theo Trapman, Jan |
| description | The PSA-Cre;Pten-loxP/loxP mouse prostate cancer model displays clearly defined stages of hyperplasia and cancer. Here, the initial stages of hyperplasia development are studied. Immunohistochemical staining showed that accumulated pAkt+ hyperplastic cells overexpress luminal epithelial cell marker CK8, and progenitor cell markers CK19 and Sca-1, but not basal epithelial cell markers. By expression profiling we identified novel hyperplastic cell markers, including Tacstd2 and Clu. Further we showed that at young age prostates of targeted Pten knockout mice contained in the luminal epithelial cell layer single pAkt+ cells, which overexpressed CK8, Sca-1, Tacstd2 and Clu; basal epithelial cells were always pAkt(-). Importantly, in the luminal epithelial cell layer of normal prostates we detected rare Clu+Tacstd2+Sca-1+ progenitor cells. These novel cells are candidate tumor initiating cells in Pten knockout mice. Remarkably, all luminal epithelial cells in the proximal region of normal prostates were Clu+Tacstd2+Sca-1+. However, in PSA-Cre;Pten-loxP/loxP mice, the proximal prostate does not contain hyperplastic foci. Small hyperplastic foci in prostates of PSA-Cre;Pten-loxP/+ mice found at old age, showed complete Pten inactivation and a progenitor marker profile. Finally, we present a novel model of prostate development and renewal, including lineage-specific luminal epithelial progenitor cells. It is proposed that Pten deficiency induces a shift in the balance of differentiation to proliferation in these cells. |
| doi_str_mv | 10.1371/journal.pone.0005662 |
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Here, the initial stages of hyperplasia development are studied. Immunohistochemical staining showed that accumulated pAkt+ hyperplastic cells overexpress luminal epithelial cell marker CK8, and progenitor cell markers CK19 and Sca-1, but not basal epithelial cell markers. By expression profiling we identified novel hyperplastic cell markers, including Tacstd2 and Clu. Further we showed that at young age prostates of targeted Pten knockout mice contained in the luminal epithelial cell layer single pAkt+ cells, which overexpressed CK8, Sca-1, Tacstd2 and Clu; basal epithelial cells were always pAkt(-). Importantly, in the luminal epithelial cell layer of normal prostates we detected rare Clu+Tacstd2+Sca-1+ progenitor cells. These novel cells are candidate tumor initiating cells in Pten knockout mice. Remarkably, all luminal epithelial cells in the proximal region of normal prostates were Clu+Tacstd2+Sca-1+. However, in PSA-Cre;Pten-loxP/loxP mice, the proximal prostate does not contain hyperplastic foci. Small hyperplastic foci in prostates of PSA-Cre;Pten-loxP/+ mice found at old age, showed complete Pten inactivation and a progenitor marker profile. Finally, we present a novel model of prostate development and renewal, including lineage-specific luminal epithelial progenitor cells. It is proposed that Pten deficiency induces a shift in the balance of differentiation to proliferation in these cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0005662</identifier><identifier>PMID: 19461893</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Androgens ; Animals ; Biomarkers - metabolism ; Cancer ; Cell proliferation ; Cells (biology) ; Deactivation ; Disease Models, Animal ; Epithelial cells ; Epithelial Cells - enzymology ; Epithelial Cells - pathology ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genetics and Genomics/Disease Models ; Genetics and Genomics/Gene Expression ; Hyperplasia ; Immunohistochemistry ; Inactivation ; Integrases - metabolism ; Kinases ; Male ; Markers ; Mice ; Mice, Knockout ; Models, Biological ; Neoplasm Proteins - metabolism ; Neoplastic Stem Cells - enzymology ; Oncology/Prostate Cancer ; Phenotype ; Progenitor cells ; Prostate - enzymology ; Prostate - pathology ; Prostate cancer ; Prostate-Specific Antigen - metabolism ; Prostatic Neoplasms - enzymology ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - pathology ; PTEN Phosphohydrolase - deficiency ; PTEN protein ; Rodents ; Stem cells ; Tumors</subject><ispartof>PloS one, 2009-05, Vol.4 (5), p.e5662-e5662</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Korsten et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Here, the initial stages of hyperplasia development are studied. Immunohistochemical staining showed that accumulated pAkt+ hyperplastic cells overexpress luminal epithelial cell marker CK8, and progenitor cell markers CK19 and Sca-1, but not basal epithelial cell markers. By expression profiling we identified novel hyperplastic cell markers, including Tacstd2 and Clu. Further we showed that at young age prostates of targeted Pten knockout mice contained in the luminal epithelial cell layer single pAkt+ cells, which overexpressed CK8, Sca-1, Tacstd2 and Clu; basal epithelial cells were always pAkt(-). Importantly, in the luminal epithelial cell layer of normal prostates we detected rare Clu+Tacstd2+Sca-1+ progenitor cells. These novel cells are candidate tumor initiating cells in Pten knockout mice. Remarkably, all luminal epithelial cells in the proximal region of normal prostates were Clu+Tacstd2+Sca-1+. However, in PSA-Cre;Pten-loxP/loxP mice, the proximal prostate does not contain hyperplastic foci. Small hyperplastic foci in prostates of PSA-Cre;Pten-loxP/+ mice found at old age, showed complete Pten inactivation and a progenitor marker profile. Finally, we present a novel model of prostate development and renewal, including lineage-specific luminal epithelial progenitor cells. It is proposed that Pten deficiency induces a shift in the balance of differentiation to proliferation in these cells.</description><subject>Androgens</subject><subject>Animals</subject><subject>Biomarkers - metabolism</subject><subject>Cancer</subject><subject>Cell proliferation</subject><subject>Cells (biology)</subject><subject>Deactivation</subject><subject>Disease Models, Animal</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - enzymology</subject><subject>Epithelial Cells - pathology</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetics and Genomics/Disease Models</subject><subject>Genetics and Genomics/Gene Expression</subject><subject>Hyperplasia</subject><subject>Immunohistochemistry</subject><subject>Inactivation</subject><subject>Integrases - metabolism</subject><subject>Kinases</subject><subject>Male</subject><subject>Markers</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Models, Biological</subject><subject>Neoplasm Proteins - 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Here, the initial stages of hyperplasia development are studied. Immunohistochemical staining showed that accumulated pAkt+ hyperplastic cells overexpress luminal epithelial cell marker CK8, and progenitor cell markers CK19 and Sca-1, but not basal epithelial cell markers. By expression profiling we identified novel hyperplastic cell markers, including Tacstd2 and Clu. Further we showed that at young age prostates of targeted Pten knockout mice contained in the luminal epithelial cell layer single pAkt+ cells, which overexpressed CK8, Sca-1, Tacstd2 and Clu; basal epithelial cells were always pAkt(-). Importantly, in the luminal epithelial cell layer of normal prostates we detected rare Clu+Tacstd2+Sca-1+ progenitor cells. These novel cells are candidate tumor initiating cells in Pten knockout mice. Remarkably, all luminal epithelial cells in the proximal region of normal prostates were Clu+Tacstd2+Sca-1+. However, in PSA-Cre;Pten-loxP/loxP mice, the proximal prostate does not contain hyperplastic foci. Small hyperplastic foci in prostates of PSA-Cre;Pten-loxP/+ mice found at old age, showed complete Pten inactivation and a progenitor marker profile. Finally, we present a novel model of prostate development and renewal, including lineage-specific luminal epithelial progenitor cells. It is proposed that Pten deficiency induces a shift in the balance of differentiation to proliferation in these cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19461893</pmid><doi>10.1371/journal.pone.0005662</doi><tpages>e5662</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Androgens Animals Biomarkers - metabolism Cancer Cell proliferation Cells (biology) Deactivation Disease Models, Animal Epithelial cells Epithelial Cells - enzymology Epithelial Cells - pathology Gene Expression Profiling Gene Expression Regulation, Neoplastic Genetics and Genomics/Disease Models Genetics and Genomics/Gene Expression Hyperplasia Immunohistochemistry Inactivation Integrases - metabolism Kinases Male Markers Mice Mice, Knockout Models, Biological Neoplasm Proteins - metabolism Neoplastic Stem Cells - enzymology Oncology/Prostate Cancer Phenotype Progenitor cells Prostate - enzymology Prostate - pathology Prostate cancer Prostate-Specific Antigen - metabolism Prostatic Neoplasms - enzymology Prostatic Neoplasms - genetics Prostatic Neoplasms - pathology PTEN Phosphohydrolase - deficiency PTEN protein Rodents Stem cells Tumors |
| title | Accumulating progenitor cells in the luminal epithelial cell layer are candidate tumor initiating cells in a Pten knockout mouse prostate cancer model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-25T15%3A30%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Accumulating%20progenitor%20cells%20in%20the%20luminal%20epithelial%20cell%20layer%20are%20candidate%20tumor%20initiating%20cells%20in%20a%20Pten%20knockout%20mouse%20prostate%20cancer%20model&rft.jtitle=PloS%20one&rft.au=Korsten,%20Hanneke&rft.date=2009-05-22&rft.volume=4&rft.issue=5&rft.spage=e5662&rft.epage=e5662&rft.pages=e5662-e5662&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0005662&rft_dat=%3Cgale_plos_%3EA473134097%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1289159893&rft_id=info:pmid/19461893&rft_galeid=A473134097&rft_doaj_id=oai_doaj_org_article_2f878e637fdf4a81b3fbf382b0564de8&rfr_iscdi=true |