Stat5 promotes metastatic behavior of human prostate cancer cells in vitro and in vivo. Endocr Relat Cancer 2010 Jun;17(2):481-93
Date
03/18/2010Pubmed ID
20233708Pubmed Central ID
PMC6260789DOI
10.1677/ERC-09-0328Scopus ID
2-s2.0-77953578552 (requires institutional sign-in at Scopus site) 108 CitationsAbstract
There are no effective therapies for disseminated prostate cancer. Constitutive activation of Stat5 in prostate cancer is associated with cancer lesions of high histological grade. We have 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 behavior of human prostate cancer cells in vitro and in vivo. Stat5 may provide a therapeutic target protein for disseminated prostate cancer.
Author List
Gu L, Vogiatzi P, Puhr M, Dagvadorj A, Lutz J, Ryder A, Addya S, Fortina P, Cooper C, Leiby B, Dasgupta A, Hyslop T, Bubendorf L, Alanen K, Mirtti T, Nevalainen MTMESH terms used to index this publication - Major topics in bold
AnimalsCarcinoma
Cells, Cultured
Gene Expression Regulation, Neoplastic
Humans
Janus Kinase 2
Male
Mice
Mice, Nude
Neoplasm Metastasis
Prostatic Neoplasms
RNA, Small Interfering
STAT5 Transcription Factor
Xenograft Model Antitumor Assays
src-Family Kinases
