Increased AKT Activity Contributes to Prostate Cancer Progression by Dramatically Accelerating Prostate Tumor Growth and Diminishing p27Kip1 Expression

摘要: The PTEN tumor suppressor gene is frequently inactivated in human prostate cancers, particularly more advanced suggesting that the AKT/protein kinase B (PKB) kinase, which negatively regulated by PTEN, may be involved cancer progression. We now show AKT activation and activity are markedly increased androgen-independent, prostate-specific antigen-positive cells (LNAI cells) established from xenograft tumors of androgen-dependent LNCaP cell line. These LNAI expression integrin-linked putatively responsible for activation/Ser-473 phosphorylation, as well phosphorylation target protein, BAD. Furthermore, p27(Kip1) cycle regulator was diminished cells, consistent with notion directly inhibits AFX/Forkhead-mediated transcription p27(Kip1). To assess impact on progression, an activated hAKT1 mutant overexpressed resulting a 6-fold increase growth. Like these transfectants showed dramatically reduced expression. Together, data implicate progression androgen independence suggest expression, has been repeatedly associated consequence activity.