期刊
SCIENTIFIC REPORTS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-019-44685-3
关键词
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资金
- National Institutes of Health [P20 GM103639, P30 CA225520]
- Department of Defense Prostate Cancer Research Program [W81XWH-13-1-0083]
- National Institutes of Health/National Cancer Institute [R01 CA154745]
The ETS transcription factor ETV1 is frequently overexpressed in aggressive prostate cancer, which is one underlying cause of this disease. Accordingly, transgenic mice that prostate-specifically overexpress ETV1 develop prostatic intraepithelial neoplasia. However, progression to the adenocarcinoma stage is stifled in these mice, suggesting that inhibitory pathways possibly preclude ETV1from exerting its full oncogenic potential. Here we provide evidence that TGF-beta/SMAD signaling represents such an inhibitory pathway. First, we discovered that ETV1 forms complexes with SMAD4. Second, SMAD2, SMAD3 and SMAD4 overexpression impaired ETV1's ability to stimulate gene transcription. Third, TGF-beta 1 inhibited ETV1-induced invasion by benign RWPE-1 prostate cells. Fourth, increased expression of SMAD3 and SMAD4 was observable in prostates of ETV1 transgenic mice. Conversely, we found that ETV1 may enhance TGF-beta signaling in PC3 prostate cancer cells, revealing a different facet of the ETV1/TGF-beta interplay. Altogether, these data provide more insights into the regulation and action of ETV1 and additionally suggest that TGF-beta/SMAD signaling exerts its tumor suppressive activity, at least in part, by curtailing the oncogenic potential of ETV1 in prostatic lesions.
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