ORIGINAL ARTICLE

Cell Research (2006): 671-677
© 2006 IBCB, SIBS, CAS All rights reserved 1001-0602/06 $ 30.00
www.nature.com/cr

Glycogen synthase kinase-3β positively regulates the proliferation of human ovarian cancer cells

Qi Cao, Xin Lu, You-Ji Feng

Correspondence: You-Ji Feng Tel: +86-21-63455050; Fax: +86-21-63455090; E-mail: fengyj4806@sohu.com Received 15 Dec 2005; revised 31 Mar 2006; accepted 24 Apr 2006

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Although glycogen synthase kinase-3 (GSK-3) might act as a tumor suppressor since its inhibition is expected to mimic the activation of Wnt-signaling pathway, GSK-3β may contribute to NF-?B activation in cancer cells leading to increased cancer cell proliferation and survival. Here we report that GSK-3β activity was involved in the proliferation of human ovarian cancer cell both in vitro and in vivo. Inhibition of GSK-3 activity by pharmacological inhibitors suppressed proliferation of the ovarian cancer cells. Overexpressing constitutively active form of GSK-3β induced entry into the S phase, increased cyclin D1 expression and facilitated the proliferation of ovarian cancer cells. Furthermore, GSK-3 inhibition prevented the formation of the tumor in nude mice generated by the inoculation of human ovarian cancer cells. Our findings thus suggest that GSK-3β activity is important for the proliferation of ovarian cancer cells, implicating this kinase as a potential therapeutic target in ovarian cancer.

Cell Research advance online publication 20 Jun 2006; doi: 10.1038/sj.cr.7310078

Keywords: glycogen synthase kinase 3β, ovarian cancer, cell proliferation, therapeutic target