Prostate Cancer Cell Growth: Stimulatory Role of Neurotensin And Mechanism of Inhibition by Flavonoids as Related to Protein Kinase C; Annual rept. 1 Jan-31 Dec 2007

摘要

The purpose is to define the relationship between neurotensin (NT) and protein kinase C (PKC) isotypes and to investigate the mechanism by which flavonoids (FLAV) inhibit NT growth signaling in PC3 cells. The long-range scope is to determine the significance of NT in the negative effects of high fat intake on PC incidence and the positive effects of diets containing FLAV. Our results show that NT-induced growth signaling involves and requires activation of several PKC isotypes (most notably PKC epsilon and delta) that arachidonic acid metabolism and EGF receptor activation participate in the NT signaling process that cell metabolism and ATP levels can influence NT receptor function and that activated PKC (most notably PKC alpha and beta) can feed back to regulate the ability of NT receptor to bind NT and to initiate signaling. FLAV was found to exert differential effects on PKC isotype activation and downregulation. Thus FLAV could alter the balance between conventional and novel PKC acbvity which could influence growth responses to NT. These findings have implications regarding mechanisms that regulate NT receptor function and the design of agents to block NT-induced growth signaling in PC.