Genistein induces the p21WAF1/CIP1 and p16INK4a tumor suppressor genes in prostate cancer cells by epigenetic mechanisms involving active chromatin modification.
In the course of modeling malignant melanoma in a tyrosinase promoter transgenic system, we developed a genetically-engineered mouse (GEM) model of invasive prostate cancers, whereby an activating mutation of BRAF(V600E)--a mutation found in approximately 10% of human prostate tumors--was targeted to the epithelial compartment of the prostate gland on the background of Ink4a/Arf deficiency.
Overexpression of p16 mRNA was found in 6/9 (67) of prostate tumors compared to the adjacent normal prostate, whereas elevated p14 and p15 levels were only observed in 2/9 (22) and 1/6 (17) of prostate cases, respectively.
Alteration of CDKN2 was observed in each prostate tumor cell line, including one with a missense mutation, and in one of three xenograft tumor tissues derived from primary carcinomas.