Up-regulation of P13K/Akt Signaling by 17 beta-estradiol through Activation of Estrogen Receptor-alpha in Breast Cancer Cells.
- Author:
Min Cheul SO
1
;
Hong Pil HWANG
;
Chang Ho LEE
;
Hyun Jo YOUN
;
Sung Hoo JUNG
;
Jae Cheun KIM
Author Information
- Publication Type:Original Article
- Keywords: Estrogen receptor; PI3K; PIP(3); 17beta-estradiol
- MeSH: Breast Neoplasms*; Breast*; Cell Line; Cell Proliferation; Estradiol*; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogens*; MCF-7 Cells; Metabolism; Phosphatidylinositol 3-Kinases; Phosphatidylinositols; Up-Regulation*
- From:Journal of Breast Cancer 2006;9(2):91-97
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: Estrogen stimulates cell proliferation in breast cancer, the biological effects of which are mediated through two intracellular receptors: estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta). However, the actual role of ERs in the proliferative action of estrogen remains to be established. It was recently found that ER activates phosphatidylinositol-3-OH kinase (PI3K), via its binding with the p85 regulatory subunit of PI3K. Therefore, possible mechanisms may include ER-mediated phosphoinositide metabolism, with the subsequent formation of phosphatidylinositol-3, 4, 5-trisphosphate (PIP(3)), which is generated from phosphatidylinositol 4, 5-bisphosphate (PIP(2)) via PI3K activation. The present study has demonstrated that 17b-estradiol (E2) up-regulates PI3K in an ERalpha, but not an ERbeta dependent manner, and also stimulates cell growth in breast cancer cells. METHODS: To study this phenomenon, we treated ER-positive MCF-7 cells and ER-negative MDA-MB-231 cells with 10 nM E2. RESULTS: The treatment of MCF-7 cells with E2 resulted in a marked increase in the expression of PI3K (p85), which was paralleled by increases in the levels of phospho-Akt (Ser-473) and PIP3. These observations were also correlated with increased E2-induced cell proliferation activity. However, no effects of E2 on breast cancer cells were observed in the MDA-MB-231 cell line, indicating the pathway of E2-mediated up-regulation of PI3K/Akt is ERalpha-dependent. CONCLUSION: These results suggest that estrogen activates PI3K/Akt signaling via an ERalpha-dependent mechanism in MCF-7 cells.
