J Breast Cancer.  2006 Jun;9(2):91-97. 10.4048/jbc.2006.9.2.91.

Up-regulation of P13K/Akt Signaling by 17 beta-estradiol through Activation of Estrogen Receptor-alpha in Breast Cancer Cells

• So MC
• Hwang HP
• Lee CH
• Youn HJ
• Jung SH
• Kim JC

• KMID: 2286625
• DOI: http://doi.org/10.4048/jbc.2006.9.2.91

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.

Keyword

Estrogen receptor; PI3K; PIP(3); 17beta-estradiol

MeSH Terms

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*
Estradiol
Estrogen Receptor alpha
Estrogen Receptor beta
Estrogens
Phosphatidylinositol 3-Kinases
Phosphatidylinositols