Keen Research Laboratory

Research

The goals of our research are to understand the mechanism controlling estrogen receptor mRNA stability in breast cancer. Current anti-hormonal therapy for breast cancer depends on inhibition of either estrogen or the Estrogen Receptor (ER). Although this therapy is quite successful, approximately 40% of ER positive tumors develop resistance and continue to grow. Because the ER is still expressed in such resistant tumors, it is still a viable target for therapy. The need exists, therefore, to identify alternative methods of targeting the ER once a tumor becomes resistant.

One such potential target is the ER mRNA. Specifically, it is necessary to identify what factors regulate stability of the ER mRNA so that they may be exploited to promote ER mRNA destabilization.

The epigenetic modulators, 5 aza 2’ deoxycytidine (AZA) and Trichostatin A (TSA), induce ER re-expression in breast cancer cells lacking ER expression. However, in those cells that do express ER, AZA and TSA treatment has the opposite effect and decreases ER levels. Our studies indicate that this may be due to a decrease in ER mRNA stability and involves decreased availability of the RNA binding protein, HuR to bind to and stabilize ER mRNA.

Current research seeks to identify how the ER mRNA is controlled and to identify regions within the 3’ untranslated region that could modify ER stability.