The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer
The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer
复制标题
控制 SOX2 在乳腺癌中致癌潜力的分子机制
DOI：
10.1074/jbc.m802917200
复制
发表时间：
2008-06-27
影响因子：
4.8
通讯作者：
Shang, Yongfeng
中科院分区：
文献类型：
--
作者：
Chen, Yupeng;Shi, Lei;Shang, Yongfeng
SOX基因编码一个高迁移率族转录因子家族，在器官发生中发挥关键作用。不同SOX蛋白的功能特异性和特定SOX因子的组织特异性在很大程度上由SOX转录因子与其他转录调节因子的差异伙伴关系决定，其中许多尚未被发现。事实上，SOX家族的所有成员都被发现在多种肿瘤中被解除调节。然而，人们对SOX蛋白致癌潜力所涉及的细胞和分子行为知之甚少。利用细胞培养实验、组织分析、分子谱分析和动物研究，我们在此报道SOX 2通过促进乳腺癌细胞中的G（1）/S转换和通过其对CCND 1基因的转录调节来促进细胞增殖和肿瘤发生。此外，我们确定了β-连环蛋白作为SOX 2的转录伴侣，并证明SOX 2和β-连环蛋白在乳腺癌细胞中协同作用于CCND 1的转录调控。我们的实验不仅确定了SOX 2在乳腺肿瘤发生中的作用，还揭示了多功能蛋白β-连环蛋白的另一种活性。
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 G(1)/S transition and through its transcription regulation of the CCND1 gene in breast cancer cells. In addition, we identified beta-catenin as the transcription partner for SOX2 and demonstrated that SOX2 and beta-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, beta-catenin.