Estrogens are critical mediators of breast tumorigenesis. This occurs via the action of estrogens on the estrogen receptor (ER), which regulates the transcriptome of breast cancer cells. Despite the long history of the search for estrogen-regulated genes in breast cancer, knowledge of the E2-regulated transcriptome and its effects is incomplete. We used Affymetrix GeneChips to profile the effects of estradiol on the expression of genes in EFF-3, EFM-19 and MCF-7 cells. In addition to many well-characterized estrogen-regulated genes, this identified a novel group of genes that have roles in vesicle trafficking, including exocytosis. Recent evidence in the literature supports a role for vesicle trafficking in tumorigenesis. We focused on five genes (SYTL5, RAB27B, SNX24, GALNT4 and SLC12A2/NKCC1/BSC2) and confirmed their estrogen-regulation using quantitative real-time PCR (qPCR). qPCR also demonstrated that these five genes were expressed in invasive breast carcinoma tissue. Immunohistochemistry showed expression of SYTL5 in cells of normal breast ductal epithelium, ductal carcinoma in-situ (DCIS) and invasive breast carcinoma. The results suggest that a significant effect of estrogens is to regulate the expression of genes that affect diverse aspects of vesicle trafficking including exocytosis.
Keywords: Breast cancer; RAB GTPase; estrogen; exocytosis; synaptotagmin-like protein; vesicle.