STAT5 promotes metastatic behaviour of human prostate cancer cells in vitro and in vivo.

Monday, 21/06/2010  |   Prostate Cancer  |  no comments

There are no effective therapies for disseminated prostate cancer. Constitutive activation of signal transducer and transcriptional activator 5 (STAT5) in prostate cancer is associated with cancer lesions of high histological grade. It has been shown that STAT5 is activated in 61% of distant metastases of clinical prostate cancer. Active STAT5 increased metastases formation of prostate cancer cells in nude mice by 11-fold in an experimental metastases assay. Active Stat5 promoted migration and invasion of prostate cancer cells, and induced rearrangement of the microtubule network. Active STAT5 expression was associated with decreased cell surface E-cadherin levels, while heterotypic adhesion of prostate cancer cells to endothelial cells was stimulated by active STAT5. Activation of STAT5 and STAT5-induced binding of prostate cancer cells to endothelial cells were decreased by inhibition of Src but not of Jak2. Gene expression profiling indicated that 21% of STAT5-regulated genes in prostate cancer cells were related to metastases, while 7.9% were related to proliferation and 3.9% to apoptosis. The work presented here provides the first evidence of Stat5 involvement in the induction of metastatic behaviour of human prostate cancer cells in vitro and in vivo.
STAT5 may provide a therapeutic target protein for disseminated prostate cancer.

Lei Gu, Paraskevi Vogiatzi, Martin Puhr, Ayush Dagvadorj, Jacqueline Lutz, Amy Ryder, Sankar Addya, Paolo Fortina, Carlton Cooper, Benjamin Leiby, Abhijit Dasgupta, Terry Hyslop, Lukas Bubendorf, Kalle Alanen, Tuomas Mirtti and Marja Nevalainen. Endocrine-related Cancer. STAT5 promotes metastatic behaviour of human prostate cancer cells in vitro and in vivo. Endocrine-related Cancer, 2010;17(2):Pp.481-93. DOI: 10.1677/ERC-09-0328

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