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Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer
BACKGROUND: The human TSPY is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY). Various molecular, pathological and transgenic mouse studies suggest that TSPY is a Y-located proto-oncogene contributing to the initiation/progression in human cancers, including germ cell tumors...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942074/ https://www.ncbi.nlm.nih.gov/pubmed/24528896 http://dx.doi.org/10.1186/2045-3701-4-9 |
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author | Kido, Tatsuo Schubert, Stephanie Hatakeyama, Shingo Ohyama, Chikara Schmidtke, Jörg Lau, Yun-Fai Chris |
author_facet | Kido, Tatsuo Schubert, Stephanie Hatakeyama, Shingo Ohyama, Chikara Schmidtke, Jörg Lau, Yun-Fai Chris |
author_sort | Kido, Tatsuo |
collection | PubMed |
description | BACKGROUND: The human TSPY is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY). Various molecular, pathological and transgenic mouse studies suggest that TSPY is a Y-located proto-oncogene contributing to the initiation/progression in human cancers, including germ cell tumors and various somatic cancers, such as prostate and liver cancer, and melanoma. The TgTSPY9 transgenic mouse line harbors a 8.2-kb human TSPY structural gene, which is tandemly integrated in the mouse Y chromosome, and expressed in a similar pattern as that of the endogenous gene in the human genome. This mouse model of human TSPY gene offers an opportunity to examine its behavior and potential contribution in various mouse models of human diseases, such as human cancers. We had investigated the expression of such TSPY-transgene in the LADY mouse model of prostate cancer, harboring a SV40 T antigen gene directed by a rat probasin promoter; and compared the expression pattern with those of endogenous TSPY gene and biomarkers in human prostate cancer specimens. RESULTS: By introducing the Y-located TSPY-transgene to the LADY mice, we had examined the expression pattern of the human TSPY during prostatic oncogenesis in this mouse model of prostate cancer. Our results showed that the TSPY-transgene was activated in selected areas of the hypercellular stroma but not in the intraepithelial cells/neoplasia in the prostates of TgTSPY9/LADY mice. Using a specific biomarker, FOXA1, for epithelial cells, we demonstrated that TSPY-positive cells proliferated exclusively in the cancerous stroma in the LADY model at late stages of tumorigenesis. In contrast, in the human situation, TSPY was predominantly co-expressed with FOXA1 in the epithelial cells of PIN lesions and FOXA1 and another cancer biomarker, AMACR, in the adenocarcinoma cells in clinical prostate cancer samples of various degrees of malignancy. CONCLUSIONS: Our data show that human TSPY could be abnormally activated during prostatic oncogenesis, and could possibly contribute to the heterogeneity of prostate cancer. The differential expression patterns of the human TSPY between the LADY mouse model and clinical prostate cancer suggest potential limitations of current mouse models for studies of either TSPY behavior in diseased conditions or prostate cancer development. |
format | Online Article Text |
id | pubmed-3942074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39420742014-03-05 Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer Kido, Tatsuo Schubert, Stephanie Hatakeyama, Shingo Ohyama, Chikara Schmidtke, Jörg Lau, Yun-Fai Chris Cell Biosci Research BACKGROUND: The human TSPY is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY). Various molecular, pathological and transgenic mouse studies suggest that TSPY is a Y-located proto-oncogene contributing to the initiation/progression in human cancers, including germ cell tumors and various somatic cancers, such as prostate and liver cancer, and melanoma. The TgTSPY9 transgenic mouse line harbors a 8.2-kb human TSPY structural gene, which is tandemly integrated in the mouse Y chromosome, and expressed in a similar pattern as that of the endogenous gene in the human genome. This mouse model of human TSPY gene offers an opportunity to examine its behavior and potential contribution in various mouse models of human diseases, such as human cancers. We had investigated the expression of such TSPY-transgene in the LADY mouse model of prostate cancer, harboring a SV40 T antigen gene directed by a rat probasin promoter; and compared the expression pattern with those of endogenous TSPY gene and biomarkers in human prostate cancer specimens. RESULTS: By introducing the Y-located TSPY-transgene to the LADY mice, we had examined the expression pattern of the human TSPY during prostatic oncogenesis in this mouse model of prostate cancer. Our results showed that the TSPY-transgene was activated in selected areas of the hypercellular stroma but not in the intraepithelial cells/neoplasia in the prostates of TgTSPY9/LADY mice. Using a specific biomarker, FOXA1, for epithelial cells, we demonstrated that TSPY-positive cells proliferated exclusively in the cancerous stroma in the LADY model at late stages of tumorigenesis. In contrast, in the human situation, TSPY was predominantly co-expressed with FOXA1 in the epithelial cells of PIN lesions and FOXA1 and another cancer biomarker, AMACR, in the adenocarcinoma cells in clinical prostate cancer samples of various degrees of malignancy. CONCLUSIONS: Our data show that human TSPY could be abnormally activated during prostatic oncogenesis, and could possibly contribute to the heterogeneity of prostate cancer. The differential expression patterns of the human TSPY between the LADY mouse model and clinical prostate cancer suggest potential limitations of current mouse models for studies of either TSPY behavior in diseased conditions or prostate cancer development. BioMed Central 2014-02-17 /pmc/articles/PMC3942074/ /pubmed/24528896 http://dx.doi.org/10.1186/2045-3701-4-9 Text en Copyright © 2014 Kido et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Kido, Tatsuo Schubert, Stephanie Hatakeyama, Shingo Ohyama, Chikara Schmidtke, Jörg Lau, Yun-Fai Chris Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer |
title | Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer |
title_full | Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer |
title_fullStr | Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer |
title_full_unstemmed | Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer |
title_short | Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer |
title_sort | expression of a y-located human proto-oncogene tspy in a transgenic mouse model of prostate cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942074/ https://www.ncbi.nlm.nih.gov/pubmed/24528896 http://dx.doi.org/10.1186/2045-3701-4-9 |
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