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
Dans Anglais
| WPRIM
| ID: wpr-49021
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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Phosphatidyl inositols
/
Région mammaire
/
Tumeurs du sein
/
Régulation positive
/
Lignée cellulaire
/
Phosphatidylinositol 3-kinases
/
Récepteur alpha des oestrogènes
/
Récepteur bêta des oestrogènes
/
Prolifération cellulaire
/
Oestradiol
langue:
Anglais
Texte intégral:
Journal of Breast Cancer
Année:
2006
Type:
Article
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