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J. Biol. Chem., Vol. 280, Issue 8, 6409-6415, February 25, 2005

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Des--carboxy Prothrombin Is a Potential Autologous Growth Factor for Hepatocellular Carcinoma^*

Mayumi Suzuki, Hidenori Shiraha, Tatsuya Fujikawa, Nobuyuki Takaoka, Naoki Ueda, Yutaka Nakanishi, Kazuko Koike, Akinobu Takaki, and Yasushi Shiratori

From the Department of Medicine and Medical Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan

Des--carboxyl prothrombin (DCP) is a well recognized tumor marker for hepatocellular carcinoma (HCC). In the present study, we demonstrate that DCP has a mitogenic effect on HCC cell lines. Purified DCP stimulated DNA synthesis of Hep3B and SK-Hep-1 cells in a dose-dependent manner. DCP was found to bind with cell surface receptor Met causing Met autophosphorylation and also to activate STAT3 signaling pathway through Janus kinase 1. Luciferase gene reporter analysis showed that DCP induced STAT3-related transcription. Small interfering RNAs against both STAT3 and Met abrogated DCP-induced cell proliferation. DCP did not affect the mitogen-activated protein kinase pathway, Myc signaling pathway, or phosphoinositide 3-kinase/Akt pathway. Based on these results, we believe that DCP acts as an autologous mitogen for HCC cell lines. The Met-Janus kinase 1-STAT3 signaling pathway may be a major signaling pathway for DCP-induced cell proliferation.

Received for publication, June 16, 2004 , and in revised form, November 15, 2004.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 81-86-235-7219; Fax: 81-86-225-5991; E-mail: hshiraha{at}md.okayama-u.ac.jp.

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This article has been cited by other articles:

				T. Fujikawa, H. Shiraha, N. Ueda, N. Takaoka, Y. Nakanishi, N. Matsuo, S. Tanaka, S.-i. Nishina, M. Suzuki, A. Takaki, et al. Des-{gamma}-carboxyl Prothrombin-promoted Vascular Endothelial Cell Proliferation and Migration J. Biol. Chem., March 23, 2007; 282(12): 8741 - 8748. [Abstract] [Full Text] [PDF]