Use of a prostate cancer xenograft model and genetically modified mice are proposed in these experiments.
For experiments with xenograft tumors, we generated C42Luc prostate cancer cells that express firefly luciferase and either wild-type BAD or BAD2SA with mutated phosphorylation sites. Growth of C42Luc xenografts was followed in live mice by noninvasive optical imaging.
To test the role of BAD phosphorylation in mouse models of prostate cancer, genetically modified mice in which endogenous BAD is replaced by mutant BAD3SA (BAD3SA knock-in mice) will be bred with mice that develop prostate cancer due to prostate-restricted expression of PTENp-/- or c-myc.
If expression of phosphorylation-deficient BAD prevents prostate cancer development, then signaling pathways that control BAD are plausible targets for anti-cancer therapy.
Subsequent efforts will be focused on identification of kinases that control BAD in prostate cancer cells and testing effects of inhibition of these kinases on tumor growth.