Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K.

摘要: We have shown previously that the AKT2 pathway is essential for cell survival and important in malignant transformation. In this study, we demonstrate elevated kinase levels of phosphatidylinositol-3-OH (PI3K) 32 80 primary breast carcinomas. The majority cases with activation are estrogen receptor alpha (ERalpha) positive, which prompted us to examine whether regulates ERalpha activity. found constitutively activated or by epidermal growth factor insulin-like factor-1 promotes transcriptional activity ERalpha. This effect occurred absence presence estrogen. Activated phosphorylates vitro vivo, but it does not phosphorylate a mutant ser-167 was replaced Ala. PI3K inhibitor, wortmannin, abolishes both phosphorylation induced AKT2. However, AKT2-induced inhibited tamoxifen completely abolished ICI 164,384, implicating AKT2-activated contributes resistance. Moreover, binds p85alpha regulatory subunit estradiol epithelial cells subsequently activates PI3K/AKT2, suggesting regulation PI3K/AKT2 through nontranscriptional ligand-independent mechanism. These data indicate between (ERalpha-PI3K/AKT2-ERalpha) may play an role pathogenesis human cancer could contribute growth.