Abstract
Abstract Loss of tumor suppressors by both epigenetic silencing and genetic deletion contributes to the development and progression of breast cancer. SOX7 is an important developmental transcription factor and its downregulation has been reported in tumor tissues and cell lines of prostate, colon and lung cancers. Our current study demonstrates that SOX7 mRNA and protein expression are downregulated in breast cancer tissues and cell lines compared to adjacent normal tissues and nontumorigenic cells, respectively. Further, we show that both hypermethylation of the SOX7 promoter and microRNAs contribute to SOX7 downregulation. SOX7 silencing by shRNAs in nontumorigenic immortal breast cells leads to increased proliferation and invasion, and they form structures resembling that of breast cancer cells in a three-dimensional culture system. Conversely, ectopic SOX7 expression inhibits proliferation, and invasion of breast cancer cells in vitro and tumor growth in vivo. Importantly, we discovered that SOX7 transcript levels positively correlated with clinical outcome of 674 breast cancer patients. Collectively, our data suggest that SOX7 acts as a tumor suppressor in breast cancer. SOX7 expression is likely regulated by multiple mechanisms and potentially serves as a prognostic marker for breast cancer patients. Citation Format: Daniel B. Stovall, Meimei Wan, Lance D. Miller, Paul Cao, Qiang Zhang, Martha Stampfer, Wennuan Liu, Jianfeng Xu, Guangchao Sui. The role and regulation of SOX7 in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr B025.
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