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Slug inhibits proliferation of human prostate cancer cells via downregulation of cyclin D1 expression
Author(s) -
Liu Jun,
Uygur Berna,
Zhang Zhonghui,
Shao Lijian,
Romero Diana,
Vary Calvin,
Ding Qiang,
Wu WenShu
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21213
Subject(s) - slug , cancer research , prostate cancer , ectopic expression , cyclin d1 , cell growth , lncap , metastasis , biology , cancer cell , cell cycle , cancer , small hairpin rna , prostate , cyclin d , gene knockdown , cell culture , medicine , genetics
BACKGROUND Slug is a transcription factor of the Snail/Slug zinc‐finger family and is implicated in metastasis of tumors, but its role in cell proliferation of prostate cancers is unclear. METHODS Expression level of Slug and other genes was examined by Western blot, RT‐PCR, and QPCR analyses. The forced expression of Slug was mediated by retroviruses and adenoviruses. Slug was downregulated by shRNA. Cell growth was measured by the MTT assay and the quick cell proliferation assay. RESULTS Here, we demonstrated that Slug expression is elevated in mouse prostate tumors, and human prostate cancer cell lines LNCaP, PC‐3, and 22RV1. Forced expression of Slug‐inhibited proliferation of prostate cancer cells PC‐3 and DU‐145. Conversely, reduced expression of Slug by shRNA promoted growth of PC‐3 cancer cells. Consistent with these data, we found that forced expression of Slug in prostate cancer cells led to G1 cell‐cycle arrest. Furthermore, ectopic expression of Slug decreased cyclin D1 expression in both PC‐3 and DU‐145 cells, and knockdown of Slug by shRNA upregulated cyclin D1 expression in these cancer cells. In addition, we demonstrated that ectopic expression of cyclin D1 relieved Slug‐mediated inhibition of proliferation of prostate cancer cells. CONCLUSIONS We provide the first compelling evidence that Slug is a negative regulator of proliferation of prostate cancer cells. Our findings in this study are distinct from the previously reported role of Slug as a promoter for tumor metastasis, and suggest that Slug is a prognostic marker and potential therapeutic target. Prostate 70: 1768–1777, 2010. © 2010 Wiley‐Liss, Inc.