A26

Tripartite motif containing protein 22 (TRIM22) is also referred to as Stimulated Transacting Factor of 50kDa (Staf50). It was originally identified as an interferon-inducible gene in human lymphoblastoid Daudi cells. It is a member of the RING-finger family of proteins and it has been implicated in antiviral response, cell growth and differentiation. To date, literature on the localization of endogenous TRIM22 is non-existent and the function of the protein in mammary epithelial cells is unknown. In this study, we found that the TRIM22 is greatly enhanced by progesterone at both the mRNA and protein levels in breast cancer cells. EGFP-tagged TRIM22 forms nuclear bodies in a variety of cell lines, with a polyclonal antibody generated against the 498 aa protein identifying similar nuclear body structures in breast cancer cells. In the MDA-MB-231-derived ABC28 cell line that stably expresses the progesterone receptor, progesterone was able to induce endogenous TRIM22 bodies to localize extensively within nucleoli. As progesterone has previously been found to inhibit growth of T47D and ABC28 cells by G0/G1 arrest, we also investigated the cell-cycle dependent changes in the distribution of TRIM22 in synchronized HELA cells stably expressing TRIM22-EGFP. We observed more cells with nucleolar TRIM22-EGFP in populations of cells in which the majority of cells (72.2%) were in the G0/G1 phase. In addition, in MCF7 cells stably expressing TRIM22-EGFP, these bodies aggregated when serum-starved or when treated with the DNA synthesis inhibitor methotrexate while serum treatment led to dispersion of these bodies into multiple smaller foci. These results suggest that TRIM22 is a dynamic protein which is likely to have a function within nucleoli. Ongoing studies on the cell cycle dependent distribution of endogenous TRIM22 and the identification of proteins interacting with TRIM22 at each phase of the cell cycle are likely to shed light on the function(s) of TRIM22.

First AACR Centennial Conference on Translational Cancer Medicine-- Nov 4-8, 2007; Singapore