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Small G‐protein RhoE is underexpressed in prostate cancer and induces cell cycle arrest and apoptosis
Author(s) -
Bektic Jasmin,
Pfeil Karina,
Berger Andreas Paul,
Ramoner Reinhold,
Pelzer Alexandre,
Schäfer Georg,
Kofler Kurt,
Bartsch Georg,
Klocker Helmut
Publication year - 2005
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.20243
Subject(s) - prostate cancer , apoptosis , medicine , prostate , cell cycle checkpoint , cancer , cell cycle , cancer research , cell cycle protein , oncology , pathology , biology , biochemistry
BACKGROUND RhoE/Rnd3, a recently described novel member of the Rho GTPases family, was discussed as a possible antagonist of the RhoA protein that stimulates cell cycle progression and is overexpressed and/or overactivated in prostate cancer. We investigated the expression of RhoE and its role in cell cycle regulation and apoptosis in the human prostate. METHODS RhoE expression in cell lines and tissue specimens was assessed by immunoblot analysis, real‐time PCR (RT‐PCR), and immunohistochemistry. To elucidate RhoE effects on the prostate, RhoE was cloned and overexpressed in DU‐145 prostate cancer. Cell cycle modulation and apoptosis was investigated by immunoblot and FACS analysis. RESULTS Immunoblot analysis showed a strong RhoE signal in both, benign epithelial and stromal cells. In contrast, almost no protein was detected in various prostate cancer cells. On RT‐PCR and microarray analysis, RhoE mRNA expression was significantly reduced in malignant tissue when compared to benign samples. RhoE immunostaining was strong in benign tissue, especially in prostate epithelial cells, whereas it was minimal or absent in malignant tissue. Forced RhoE overexpression in a prostate cancer cell line inhibits the expression of two proteins essential for G2/M transition, namely CDC2 and cyclin B1, and induces G2/M arrest. In addition, apoptotic cell death as measured by a cleavage product of caspase 3 is significantly increased in RhoE‐overexpressing cells. CONCLUSION In conclusion, our findings suggest RhoE as a tumor suppressor gene that is downregulatated early in the development of prostate cancer. © 2005 Wiley‐Liss, Inc.