? Progression to androgen-independent prostate tumor is still the major cause of prostate cancer (CAP) related death. Design of preventive and therapeutic agents that can effectively delay or prevent progression of androgen-independent prostate tumor from androgen-dependent prostate tumor has been one of the priorities in CaP research. Previous studies have suggested that soybean contains bioactive components that inhibit the progression of CaP. This pilot application is focused on evaluating the preventive effects of soy isoflavone genistein and soy phytochemical concentrate (SPC) on prostate tumor progression to androgen-independence and on identifying the molecular targets of genistein and SPC actions. The hypothesis is that bioactive soy components may prevent or delay the progression of androgen-independent and hormone-refractory CaP. ? ? Specific Aim 1 is to determine the dose-dependent effects of genistein and SPC on prevention of CaP progression to androgen-independent phenotype from androgen-dependent phenotype. An animal model for orthotopic progression of androgen-sensitive CaP to androgen-independent CaP will be used. Final primary tumor weight will be used as the primary outcome to determine the dose-dependent effects of genistein or SPC on prevention of progression to androgen-independent prostate tumors. Both lymph nodes metastases and lung metastases will be used to determine the dose-dependent effects of genistein or SPC on prevention of metastasis during progression to androgen-independence.
Specific Aim 2 is to apply cDNA microarray assays to identify prostate tumor genes that may be responsible for the effects of genistein and SPC on prevention of androgen-independent prostate tumor. Tumor samples derived from the animal study in Specific Aim 1 will be used to prepare total RNA for cDNA microarray assays. By performing data mining and analysis, we expect to identify several genes that may be responsible for the progression of androgen-independent prostate tumors and are sensitive to the genistein and/or SPC actions. These verified genes may be candidates of surrogate endpoint markers for evaluating the efficacy of soy prevention trials on CaP progression. Results derived from this pilot application will shed insight into the potential application of soy bioactive components to the prevention of CaP progression to androgen-independent phenotype and the understanding of molecular mechanisms of action. ? ?
