Estrogen and progesterone are essential for the development of normal mammary gland. They are also implicated in the development of breast cancer. The function of progesterone seems to come second after estrogen. Biologically, the expression of progesterone receptor (PR) in the target tissue is primarily dependent on the presence of estrogens so progesterone is only active in cells treated with estrogen. Evolutionarily, estrogen was the first steroid receptor to evolve and this was followed by a progesterone receptor. Our primary area of interest is to understand how PR modulate the activity of ER and what the significance of this modulation is in the context of breast cancer treatment. We are also characterizing the function of some novel progesterone-regulated genes in order to understand the down-stream pathways of PR. Tetratricopeptide repeat domain 9 (TTC9) codes for a 25 kD protein that was recently identified by our laboratory. It was also found an estrogen-inducible gene in mice. Our current research is to study the interacting proteins for TTC9 and to generate TTC9 knockout mice for functional studies. Tripartite motif-containing 22 (TRIM22) belongs to TRIM family of proteins that have a conserved domain structure consisting of a RING domain, followed by one or two B-boxes domains and a Coiled-coil domain (CC). TRIM22 was initially discovered as an interferon-inducible gene which was later found to inhibit clonogenic growth in leukemic cells, but it is better known for its anti-viral properties. We have found that TRIM22 protein form distinct nuclear bodies and the TRIM22 bodies undergo dynamic changes during cell cycle progression. Furthermore, it is immensely under-expressed in breast cancer cells compared to normal mammary epithelial cells. The current research effort for TRIM22 is directed to understand how it is inactivated in breast cancer cells and the molecular mechanism of action of TRIM22 in normal mammary epithelial cells.