SRY-related HMG-box gene 2 (SOX2) is one of the key regulatory genes that maintain the pluripotency and self-renewal properties in embryonic stem cells. Here we used immunohistochemistry to analyze the expression of SOX2 in human prostate tissues and found it contributed to tumorigenesis and correlated with histologic grade and Gleason score. We further investigated SOX2's function in cell growth and apoptosis process by using a human prostate cancer cell line DU145 with SOX2 overexpression or down-regulation. Cell cycle assay revealed that SOX2 promoted cell growth and increased the percentage of cells in S phase. In vitro and in vivo xenograft experiments in NOD/SCID mice further demonstrated that SOX2 increased the apoptosis-resistant properties of DU145 cells with decreased function of store-operated Ca(2+) entry and reduced expression of Orai1 at both mRNA and protein levels, suggesting a potential mechanism that contributes to the anti-apoptotic property of SOX2. To our knowledge, this study is the first to investigate SOX2's function in tumorigenesis and apoptosis of human prostate cancer and to elucidate its regulatory effect on the activity of store-operated Ca(2+) channels. Our results support the concept that SOX2 has the potential to be a significant marker to evaluate the progression of prostate cancer and serve as a potentially useful target for prostate cancer therapy.

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SOX2 is one of the key regulatory genes to maintain the pluripotency and unlimited cell growth properties in embryonic stem cells. Recently, more and more researches on cancer stem cell (CSC) support the hypothesis that CSC is the progenitor of cancer cells and contributes to the chemoresistant properties of cancer cells. Although previous study showed SOX2 contributed to the tumorigenic properties in breast and gastric tumor, its function in prostate cancer and apoptosis are still largely unknown. In this study, we used immunohistochemistry method to analyze the expression of SOX2 in prostate cancer tissues and found that the degree of SOX2 staining increased when the Gleason histological grade went higher. We further investigate SOX2's function in cell growth and apoptosis process by using human prostate cancer cells-DU145 with SOX2 overexpression or down-regulation by shRNA. We found that SOX2 increased cell growth and the percentage of cells in S phase in cell cycle assay, it also increased the apoptosis resistant properties of DU145 with reduced mRNA expression of Orai1, STIM1 and decreased store-operated Ca2+ entry (SOCE) activity and cytosolic Ca2+ concentration. This study first investigated SOX2's function in apoptosis process of prostate cancer and elucidated SOX2's regulatory effect on SOCE activity. Our study supports the concept that targeting SOX2 to increase the SOCE activity may be a potential strategy in prostate cancer therapy. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1216.

Ectopic expression of SOX2 has been reported in a variety of tumor tissues and contributes to cell proliferation and tumorigenesis by transcriptional regulation of the target genes; however the role of SOX2 in tumor metastasis and the underlying mechanisms remain largely elusive. Here we used immunohistochemistry to analyze the expression of SOX2 in the tissues of human breast and lymph nodes and found that SOX2 was highly expressed in breast cancer tissues and the metastasised lymph node, also the expression of SOX2 was closely correlated with the TNM stage and histological grade. We further demonstrated that SOX2 improved the migration and invasion properties of breast cancer and prostate cancer cells by facilitating the process of epithelial-mesenchymal transition (EMT). Investigation of the molecular mechanism revealed that SOX2 regulated EMT by β-catenin signaling pathway. Our findings prove that SOX2 plays a pivotal role in the metastasis of human breast cancer and prostate cancer and suggest that SOX2 has the potential to be developed as the diagnosis marker for breast and prostate cancer metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1488. doi:10.1158/1538-7445.AM2011-1488