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The Journal of Biological Chemistry
Year: 2008  |  Volume: 283  |  Issue: 26  |  Page No.: 17969 - 17978

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

Yupeng Chen, Lei Shi, Lirong Zhang, Ruifang Li, Jing Liang, Wenhua Yu, Luyang Sun, Xiaohan Yang, Yan Wang, Yu Zhang and Yongfeng Shang    

Abstract: 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.

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