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Nek2 as an Effective Target for Inhibition of Tumorigenic Growth and Peritoneal Dissemination of Cholangiocarcinoma

Divisions of ¹ Surgical Oncology and ² Cancer Biology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan

Requests for reprints: Michinari Hamaguchi, Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65-Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Phone: 81-52-744-2462; Fax: 81-52-744-2464; E-mail: mhamagu{at}med.nagoya-u.ac.jp.

We investigated the role of Nek2, a member of the serine/threonine kinase family, Nek, in the tumorigenic growth of cholangiocarcinoma cells. Expression of Nek2 is elevated in cholangiocarcinoma in a tumor-specific manner as compared with that of normal fibroblast cells. Expression of exogenous Nek2 did not perturb the growth of cholangiocarcinoma cells, whereas suppression of the Nek2 expression with siRNA resulted in the inhibition of cell proliferation and induced cell death. In xenograft-nude mouse model, s.c. injection of Nek2 siRNA around the tumor nodules resulted in reduction of tumor size as compared with those of control siRNA injection. In peritoneal dissemination model, Nek2 siRNA–treated mice showed statistically longer survival periods in comparison with those of the control siRNA–treated mice. Taken together, our data indicate a pivotal role of Nek2 in tumorigenic growth of cholangiocarcinoma. [Cancer Res 2007;67(20):9637–42]

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