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J. Biol. Chem., Vol. 283, Issue 26, 17969-17978, June 27, 2008

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The Molecular Mechanism Governing the Oncogenic Potential of SOX2 in Breast Cancer^*

From the Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100083, China

SOX genes encode a family of high-mobility group transcription factors that play critical roles in organogenesis. The functional specificity of different SOX proteins and the tissue specificity of a particular SOX factor are largely determined by the differential partnership of SOX transcription factors with other transcription regulators, many of which have not yet been discovered. Virtually all members of the SOX family have been found to be deregulated in a wide variety of tumors. However, little is known about the cellular and molecular behaviors involved in the oncogenic potential of SOX proteins. Using cell culture experiments, tissue analysis, molecular profiling, and animal studies, we report here that SOX2 promotes cell proliferation and tumorigenesis by facilitating the G₁/S transition and through its transcription regulation of the CCND1 gene in breast cancer cells. In addition, we identified β-catenin as the transcription partner for SOX2 and demonstrated that SOX2 andβ-catenin act in synergy in the transcription regulation of CCND1 in breast cancer cells. Our experiments not only determined a role for SOX2 in mammary tumorigenesis but also revealed another activity of the multifunctional protein, β-catenin.

Received for publication, April 16, 2008 , and in revised form, May 1, 2008.

^* This work was supported in part by Grants 30621002 and 30470912 (to Y. S.), 30500263 (to J. L.), and 30600319 (to W. Y.) from the National Natural Science Foundation of China and Grants 863 (Program: 2006AA02Z466) and 973 (Program: 2005CB522404 and 2007CB914503) (to Y. S.) from the Ministry of Science and Technology of China. 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental methods and Fig. S1.

¹ To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China. Tel.: 86-10-82805118; Fax: 86-10-82801355; E-mail: yshang{at}hsc.pku.edu.cn.

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