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Research Paper

Possible Roles of Vinexinβ in Growth and Paclitaxel Sensitivity in Human Prostate Cancer PC-3 Cells

Kosuke Mizutani, Koh-ichi Nagata, Hidenori Ito, Hidetoshi Ehara, Yoshinori Nozawa and Takashi Deguchi

volume 6 | issue 11

November 2007
Pages: 1800 - 1804

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Purpose: Vinexinβ is an adaptor protein supposed to play pivotal roles in cell adhesion, cytoskeletal organization and signaling. Vinexinβ is reported to be phosphorylated by extracelluler signal-regulated kinase (ERK) and the phosphorylation has been shown to be involved in cell adhesion, migration and growth. However, physiological function as well as pathophysiological relevance of vinexinβ in cancer cells is almost unknown. Methods: By use of biochemical and cell biological techniques, we analyzed the effects of over-expression or RNAi-mediated silencing of vinexinβ on the growth and paclitaxel sensitivity in a prostate cancer cell line PC-3. Results: Vinexinβ was highly expressed in androgen-independent prostate cancer cell lines, PC-3 and DU145, but not in androgen-dependent LNCaP cells. We established two PC-3 cell lines, PC-3/Vinβ#1 and #2, stably expressing GFP-tagged vinexinβ and found that growth rate of these lines was significantly increased compared to a mock-transfected cell line. In addition, we found that PC-3/Vinβ#1 and #2 became resistant to the treatment with 100 nM paclitaxel for 48 h. On the other hand, when siRNA-mediated vinexinβ gene silencing was performed, PC-3 cell growth was suppressed. In addition, by vinexinβ silencing, PC-3 cells became significantly sensitized to 10 nM paclitaxel treatment for 48 h. Conclusions: Vinexinβ plays an important role in PC-3 cell growth, and abrogation of vinexinβ may be effective for therapeutic cell death and enhanced chemotherapy sensitization in androgen-independent prostate cancer cells.


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