Cancer is usually treated at time of diagnosis, and chemoprevention is not usually considered until adulthood. Our hypothesis is that early windows of development play a key role in protecting against prostate cancer. This is based on prostate and breast cancer epidemiological reports and our demonstration that genistein, a phytoestrogen component of soy, given only prepubertally, suppressed chemically-induced mammary cancer in rats. Our most recent data has shown that dietary exposure to physiological concentrations of genistein, starting at puberty, suppressed the development of spontaneously developing prostate cancer in """"""""TRAMP"""""""" mice (TRAnsgenic Mouse Prostate adenocarcinoma). Also, we have observed that dietary genistein exposure down-regulated androgen receptor, estrogen receptor-alpha, IGF-I and ERK-1 mRNAs, and EGF-receptor expression in prostates of mice and rats. This suggests that genistein may be effective in modulating sex steroid and growth factor signaling. We hypothesize that an important component of reduced susceptibility to prostate cancer is dependent on """"""""imprinting."""""""" We believe that imprinting in the prostate with genistein will determine the biochemical """"""""blue print"""""""" of how the prostate will respond to future hormone and growth factor stimuli in adults.
The aims are: 1) to determine the most effective developmental period for genistein chemoprevention of prostate cancer in TRAMP mice; 2) to investigate prostate gland morphology as the cellular mechanism of action; 3) to investigate genistein regulation of sex steroid receptors and specific growth factor receptors and ligands as mechanisms of chemoprevention; 4) to determine if activation of estrogen receptors-alpha and-beta is a required primary event for the action of genistein in the prostate; and 5) to investigate DNA methylation of sex steroid receptors as the imprinting mechanism. The importance of this lies in the need to know, prior to initiation of clinical trials, if early exposure to an appropriate imprinting agent such as genistein, will enhance protection against prostate cancer. We propose this in a dietary model at """"""""physiological concentrations.""""""""
| Wang, Jun; Eltoum, Isam-Eldin; Lamartiniere, Coral A (2004) Genistein alters growth factor signaling in transgenic prostate model (TRAMP). Mol Cell Endocrinol 219:171-80 |
| Fritz, Wayne A; Cotroneo, Michelle S; Wang, Jun et al. (2003) Dietary diethylstilbestrol but not genistein adversely affects rat testicular development. J Nutr 133:2287-93 |
| Fritz, Wayne A; Eltoum, Isam-Eldin; Cotroneo, Michelle S et al. (2002) Genistein alters growth but is not toxic to the rat prostate. J Nutr 132:3007-11 |
