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KMID : 1134120060090020091
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Journal of Breast Cancer
2006 Volume.9 No. 2 p.91 ~ p.97
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Up-regulation of PI3K/Akt signaling by 17b-estradiol through activation of estrogen receptor-a in breast cancer cells
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So Min-Cheul
Hwang Hong-Pil
Lee Chang-Ho
Youn Hyun-Jo
Jung Sung-Hoo
Kim Jae-Chun
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Abstract
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Purpose: Estrogen stimulates cell proliferation in breast cancer, the biological effects of which are mediated through two intracellular receptors: estrogen receptor-alpha (ER) and estrogen receptor-beta (ER?). 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 (PIP3), which is generated from phosphatidylinositol 4, 5-bisphosphate (PIP2) via PI3K activation. The present study has demonstrated that 17b-estradiol (E2) up-regulates PI3K in an ERa, but not an ERb 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 ERa- dependent.
Conclusion: These results suggest that estrogen activates PI3K/Akt signaling via an ERa-dependent mechanism in MCF-7 cells. (J Breast Cancer 2006;9:91-97)
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KEYWORD
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Estrogen receptor, PI3K, PIP3, 17b-estradiol
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