245 - p27Kip1 is Upregulated in UMSCV-4 Cells Corresponding to Entering a State of Quiescence when Treated with Clobetasol.

Quiescence, the temporary exit from the cell cycle, presents therapeutic challenges to cancer management since it allows evasion of chemotherapy and radiotherapy treatment. Essential to the study of quiescence in carcinogenesis is an established model system. Our studies have found that clobetasol treatment of the vulvar cancer cell line, UMSCV-4 causes these cells to enter a state of dormancy. Subsequent removal of the cells from clobetasol show a return to normal cell proliferation, even after dormancy for 3 months. p27^Kip1 protein is elevated in quiescent cells and has been used as a marker for entry into quiescence. Using both antibodies against p27^Kip1 and transfection of a modified p27^Kip1 into the UMSCV-4 cells we have found that p27^Kip1 is upregulated by addition of clobetasol, reflecting that quiescence is being activated in the clobetasol treated UMSCV-4 cells. Cells that were incubated in clobetasol for three months and then removed from clobetasol (UMSCV-4 LT), allowing them to reenter the cell cycle no longer expressed p27^Kip1 upon re-exposure to clobetasol. This establishes the UMSCV-4 cells as a good model system for the study of clobetasol induced quiescence in vulvar squamous epithelial cells. The importance of this work is underscored by the observation that clobetasol is often used to treat a common inflammatory disease of the vulva known as vulvar lichen sclerosus (VLS) and up to 65% of vulvar carcinomas arise in the background of VLS.