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Title: USING DNA MICROARRAY ANALYSES TO ELUCIDATE THE EFFECTS OF GENISTEIN IN ANDROGEN-DEPENDENT PROSTATE CANCER CELLS: IDENTIFICATION OF NOVEL TARGETS FOR CANCER PREVENTION

Author
item Takahashi, Yoko
item LAVIGNE, JACKIE - NCI,NIH,BETHESDA,MD
item HURSTING, STEPHEN - NCI,NIH,BETHESDA,MD
item CHANDRAMOULI, GADISETTI - NCI,NIH,BETHESDA,MD
item PERKINS, SUSAN - NCI,NIH,BETHESDA,MD
item BARRETT, CARL - NCI,NIH,BETHESDA,MD
item Wang, Thomas - Tom

Submitted to: Molecular Carcinogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/11/2004
Publication Date: 10/1/2004
Citation: Takahashi, Y., Lavigne, J.A., Hursting, S.D., Chandramouli, G.V., Perkins, S.N., Barrett, C., Wang, T.T. 2004. Using dna microarray analyses to elucidate the effects of genistein in androgen-dependent prostate cancer cells: identification of novel targets for cancer prevention. Molecular Carcinogenesis, Vol. 1 (2), pp. 108-119.

Interpretive Summary: Many studies have correlated the consumption of soy-rich diets with a decreased risk of developing hormone-dependent cancers, including prostate cancer. Genistein is a candidate prostate cancer preventive phytochemical found at high levels in soybeans and soy foods. To better understand the molecular mechanisms underlying the beneficial effects of genistein on prostate cancer prevention, we utilized a DNA microarray approach to examine the effects of genistein, at doses in the physiologic range, on global gene expression patterns in androgen-dependent cancer cells. DNA microarray analyses were performed on androgen-dependent LNCaP human prostate cancer cells exposed to 0, 1, 5 or 25 M genistein. We found a concentration-dependent modulation of multiple cellular pathways that are important in prostate carcinogenesis. Interestingly, the androgen receptor-mediated pathways, in particular, appeared to be modulated by genistein at the lowest concentrations. Exposure to the male sex hormone androgen is considered a risk factor for development of prostate cancer. Based on these results, we propose that the regulation of androgen receptor-mediated is potentially the most relevant chemopreventive mechanism for genistein administered at physiologic levels. This work will provide novel information for cancer research scientists regarding molecular targets and mechanisms of action of soy-derived phytochemicals and will serve as important bases for future design of cancer preventive strategy.

Technical Abstract: Many studies have correlated the consumption of soy-rich diets with a decreased risk of developing hormone-dependent cancers, including prostate cancer. Genistein is a candidate prostate cancer preventive phytochemical found at high levels in soybeans and soy foods. To better understand the molecular mechanisms underlying the beneficial effects of genistein on prostate cancer prevention, we utilized a DNA microarray approach to examine the effects of genistein at doses in the physiologic range on global gene expression patterns in androgen-dependent cancer cells. Microarray analyses were performed on androgen-dependent LNCaP human prostate cancer cells exposed to 0, 1, 5 or 25 M genistein. We found a concentration-dependent modulation of multiple cellular pathways that are important in prostate carcinogenesis. Interestingly, the androgen receptor-mediated pathways, in particular, appeared to be modulated by genistein at the lowest concentrations. Based on these results, we proposed that the regulation of androgen receptor-mediated is potentially the most relevant chemopreventive mechanism for genistein administered at physiologic levels.