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Estrogen regulates vesicle trafficking gene expression in EFF-3, EFM-19 and MCF-7 breast cancer cells

Lookup NU author(s): Paul Wright, Dr Felicity May, Dr Steven Darby, Rehan Saif, Professor Thomas Lennard, Professor Bruce Westley


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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. (IJCEP812004).

Publication metadata

Author(s): Wright PK, May FEB, Darby S, Saif R, Lennard TWJ, Westley BR

Publication type: Article

Publication status: Published

Journal: International Journal of Clinical and Experimental Pathology

Year: 2009

Volume: 2

Issue: 5

Pages: 463-475

ISSN (electronic): 1936-2625

Publisher: E-Century Publishing Corporation