Abstract
Prostaglandin E2 (PGE2), a product of cyclooxygenase-2 (COX-2) enzymatic activity, induced aromatase activity which converts androgens to estrogens and mediates cell biological function. However, the relationship between estradiol (E2), COX-2 and PGE2 signaling pathway in Her-2/neu breast cancer cell was still unclear. In this report, we elucidate the mechanisms that mediate COX-2 expression and define the relationship of E2 and PGE2 with clinicopathological characteristics in breast cancer patients. The results were presented to demonstrate that the high level of PGE2 (P=0.02) and E2 (P=0.09) was significantly correlated with histological grade. To further investigate the signaling pathways mediating COX-2 gene expression, the experiments were performed in human breast cancer cell lines. In vitro study we found that time and dose courses of COX-2 were induced by E2 treatment in human breast adenocarcinoma cell lines Her-18(Her-2/neu stable expression cell lines), but not in MCF-7 cell lines. Furthermore, the effect was eliminated by pretreatment with MAPK, P38, PI3K, Her-2 inhibitor and estrogen antagonist ICI 182,780. Collectively, our data indicate that MAPK/PI3K/COX-2 is the functional signaling pathway intermediates linking Her-2/neu and E2 and suggest that inhibitors of PGE2 synthesis will suppress cancer cell proliferation in human breast cancer cell lines.
Citation Format: Eing-Mei Tsai, Tsung-Hua Hsieh. Estradiol induced prostaglandin E2 expression to regulate cell proliferation through MAPK/PI3K/COX2 signal pathway in Her2/neu breast cancer cell. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A42.
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