Possible roles of vinexinbeta in growth and paclitaxel sensitivity in human prostate cancer PC-3 cells.
OBJECTIVE
Vinexinbeta is an adaptor protein supposed to play pivotal roles in cell adhesion, cytoskeletal organization and signaling. Vinexinbeta 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 vinexinbeta in cancer cells is almost unknown.


METHODS
By use of biochemical and cell biological techniques, we analyzed the effects of overexpression or RNAi-mediated silencing of vinexinbeta on the growth and paclitaxel sensitivity in a prostate cancer cell line PC-3.


RESULTS
Vinexinbeta 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/Vinbeta#1 and #2, overexpressing GFP-tagged vinexinbeta 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/Vinbeta#1 and #2 became resistant to the treatment with 100 nM paclitaxel for 48 h. On the other hand, when siRNA-mediated vinexinbeta gene silencing was performed, PC-3 cell growth was suppressed. In addition, by vinexinbeta silencing, PC-3 cells became significantly sensitized to 10 nM paclitaxel treatment for 48 h.


CONCLUSIONS
Vinexinbeta plays an important role in PC-3 cell growth, and abrogation of vinexinbeta may be effective for therapeutic cell death and enhanced chemotherapy sensitization in androgen-independent prostate cancer cells.
Mizutani
Kosuke
K
Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan. islandminami@yahoo.co.jp
Nagata
Koh-ichi
K
Ito
Hidenori
H
Ehara
Hidetoshi
H
Nozawa
Yoshinori
Y
Deguchi
Takashi
T
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020868:Gene Silencing; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D017239:Paclitaxel / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D034622:RNA Interference
D048868:Adaptor Proteins, Signal Transducing; D000972:Antineoplastic Agents, Phytogenic; D009124:Muscle Proteins; C486523:SORBS3 protein, human; D017239:Paclitaxel