Up-regulation of P13K/Akt Signaling by 17 beta-estradiol through Activation of Estrogen Receptor-alpha in Breast Cancer Cells / 한국유방암학회지
Journal of Breast Cancer
; : 91-97, 2006.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-49021
Responsible library:
WPRO
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.
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Phosphatidylinositols
/
Breast
/
Breast Neoplasms
/
Up-Regulation
/
Cell Line
/
Phosphatidylinositol 3-Kinases
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Cell Proliferation
/
Estradiol
Language:
English
Journal:
Journal of Breast Cancer
Year:
2006
Document type:
Article