SLC5A8-Mediated Switching of STAT3 from a Pro-Oncogenic Signal into a Proapoptotic Signal in Breast Cancer. Revision.

摘要

The purpose of this study is to establish the functional significance of SLC5A8, a butyrate transporter and tumor suppressor, in STAT3 associated cellular apoptosis. In normal mammary epithelium both STAT3 and SLC5A8 are active and functional and thus it maintains the cellular homeostasis by regulation of cellular apoptosis. However, many cancers including breast cancer is associated with constitutively active STAT3 with inactive SLC5A8 expression.Either the functional co-operation between the STAT3 and SLC5A8 in normal mammary epithelium or the functional redundancy between STAT3 and SLC5A8 in human breast cancer is not known. In order to understand the functional implication of SLC5A8 in STAT3 associated cellular apoptosis and pro-oncogenic potential in human mammary epithelium, we have developed a stable cell lines in human normal mammary epithelial cell line that express the functional STAT3 and SLC5A8, HMEC and MCF10A, with constitutively active STAT3 (STAT3C). Further, we have developed a stable cell line in these cells with SLC5A8shRNA. To check the functional importance of SLC5A8 in STAT3 associated apoptosis, we have developed a stable cell lines in human breast cancer cell line MCF7, which constitutively express STAT3 with undetectable expression of SLC5A8, with functional SLC5A8. We are using these stable cell lines to delineate the molecular signaling involved in regulation of STAT3 and SLC5A8 in human mammary epithelium.