Prostate cancer is usually treated by castration in order to eliminate tumor-promoting androgens from the body. However, most cancers come back as castration-resistant tumors for which current treatments are ineffective. These tumors typically express a version the androgen receptor that has become independent of androgens and has an altered function in the cell nucleus. We recently identified a gene, GATA3 that is sufficient to block prostate cancer progression in mice. We found that GATA3 is necessary for the normal localization of the androgen receptor to the cell nucleus where it normally works. In tumors, the androgen receptor is sent back to the nucleus while GATA3 is inactivated.
We believe that GATA3 is necessary to bring the androgen receptor to the nucleus of normal prostatic cells where they cooperate to regulate the expression of important genes and that the deregulation of this process promotes tumor progression. This proposal will test this idea using prostatic cells, mice and human cancer tissues.

These experiments will help understand how the androgen receptor becomes insensitive to androgen and what is responsible for its altered activity in cancer cells. These results may therefore lead to the identification of new therapeutic targets to treat advanced prostate cancer.