Expression and Promoter Methylation of p16Ink4A During Estrogen-Induced Mammary Carcinogenesis in the ACI Rat

摘要

Breast cancer is one of the leading causes of death for women in the United States and estrogen exposure has been hypothesized to be involved in the development of this cancer. Our lab is studying the ACI rat, an estrogen- induced breast cancer animal model to begin to elucidate estrogen's role in breast cancer. The ACI rat develops mammary cancer after prolonged exposure to l7beta-estradiol, while the BN and genetically related COP rats do no. We have identified several polymorphisms in the promoter region of p16cdkn2a between the ACI rat and either the BN or COP rats. Several of these polymorphisms are in key regions of transcriptional control for p16cdkn2a and similar polymorphisms have been identified in the human. In addition, we have shown in the ACI rat that the p16cdkn2a message levels are down regulated and that this down regulation is due to hypermethylation of the promoter region. Further research will focus on the determination of the role of these polymorphisms in the down regulation and methylation of p16cdkn2a and the timing of this down regulation and methylation.