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Biochem Pharmacol. 1999 Aug 1;58(3):425-30.

Role of AKT1 in 17beta-estradiol- and insulin-like growth factor I (IGF-I)-dependent proliferation and prevention of apoptosis in MCF-7 breast carcinoma cells.

Author information

1
Department of Pharmacology, and Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.

Abstract

AKT1 (c-AKT, PKBalpha) is the cellular homolog of the protein-serine/threonine kinase oncogene, v-akt. AKT1 is activated through the insulin and platelet-derived growth factor signaling pathways in transfected fibroblasts, but little is known about the regulation of endogenous AKT1 in tumor cells. AKT1 levels were higher in a panel of human breast carcinoma cell lines than in breast epithelial cells, particularly those with higher HER2 expression. AKT1 activity was increased by either estradiol or IGF-I in estrogen-dependent MCF-7 cells, and both factors acted synergistically to increase AKT1 activity and promote cell proliferation. Stimulation of AKT1 activity by estradiol and IGF-I was blocked by the antiestrogen ICI 182780 and by the phosphatidylinositol-3-kinase inhibitor wortmannin. MCF-7 cells transfected with AKT1 exhibited partial estrogen- and IGF-I-independent growth and were more responsive to the combination of IGF-I and estradiol. AKT1-overexpressing MCF-7 cells were less sensitive to apoptosis induced by wortmannin. These findings suggest that AKT1 is a downstream effector of estrogen- and IGF-I-dependent proliferation and survival in hormone-responsive MCF-7 breast carcinoma cells.

PMID:
10424760
DOI:
10.1016/s0006-2952(99)00125-2
[Indexed for MEDLINE]

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