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

• Published in: Biochemical pharmacology 1999-08, Vol.58 (3), p.425-430
• Main Authors: Ahmad, Shakeel, Singh, Nadia, Glazer, Robert I.
• Format: Article
• Language: English
• Subjects: AKT1; apoptosis; Biological and medical sciences; estradiol; Fundamental and applied biological sciences. Psychology; Gene expression; IGF-I; MCF-7 cells; Molecular and cellular biology; Molecular genetics
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(99)00125-2

AKT1 (c-AKT, PKBα) 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.