SOX9 elevation in the prostate promotes proliferation and cooperates with PTEN loss to drive tumor formation Journal Article
| Authors: | Thomsen, M. K.; Ambroisine, L.; Wynn, S.; Cheah, K. S. E.; Foster, C. S.; Fisher, G.; Berney, D. M.; Møller, H.; Reuter, V. E.; Scardino, P.; Cuzick, J.; Ragavan, N.; Singh, P. B.; Martin, F. L.; Butler, C. M.; Cooper, C. S.; Swain, A. |
| Article Title: | SOX9 elevation in the prostate promotes proliferation and cooperates with PTEN loss to drive tumor formation |
| Abstract: | Dysregulation of tissue development pathways can contribute to cancer initiation and progression. In murine embryonic prostate epithelia, the transcription factor SOX9 is required for proper prostate development. In this study, we examined a role for SOX9 in prostate cancer in mouse and human. In Pten and Nkx3.1 mutant mice, cells with increased levels of SOX9 appeared within prostate epithelia at early stages of neoplasia, and higher expression correlated with progression at all stages of disease. In transgenic mice, SOX9 overexpression in prostate epithelia increased cell proliferation without inducing hyperplasia. In transgenic mice that were also heterozygous for mutant Pten, SOX9 overexpression quickened the induction of high-grade prostate intraepithelial neoplasia. In contrast, Sox9 attenuation led to a decrease proliferating prostate epithelia cells in normal and homozygous Pten mutant mice with prostate neoplasia. Analysis of a cohort of 880 human prostate cancer samples showed that SOX9 expression was associated with increasing Gleason grades and higher Ki67 staining. Our findings identify SOX9 as part of a developmental pathway that is reactivated in prostate neoplasia where it promotes tumor cell proliferation. ©2010 AACR. |
| Keywords: | immunohistochemistry; adult; controlled study; protein expression; nonhuman; mutant protein; protein function; neoplasm; ki 67 antigen; cell proliferation; ki-67 antigen; animal cell; mouse; mouse mutant; animals; mice; mice, knockout; animal tissue; gene overexpression; gene expression profiling; animal experiment; animal model; homeodomain proteins; cancer model; transgenic mouse; mice, transgenic; transcription factors; prostate cancer; kaplan-meiers estimate; gleason score; prostatic neoplasms; gene expression regulation, neoplastic; prostate; reverse transcriptase polymerase chain reaction; hyperplasia; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; pten phosphohydrolase; staining; prostate epithelium; tissue array analysis; epithelium; transcription factor sox9; sox9 transcription factor |
| Journal Title: | Cancer Research |
| Volume: | 70 |
| Issue: | 3 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2010-02-01 |
| Start Page: | 979 |
| End Page: | 987 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-09-2370 |
| PUBMED: | 20103652 |
| PROVIDER: | scopus |
| PMCID: | PMC3083842 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: CNREA" - "Source: Scopus" |
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