Ovarian granulosa cell tumors express a functional membrane receptor for anti-Mullerian hormone in transgenic mice

Anti-Mullerian hormone inhibits granulosa cell growth and function. Both an ti-Mullerian hormone and its type II receptor are expressed in normal granu losa cells. We show by histologic and molecular analyses that ovarian tumor s developing in transgenic mice, obtained by targeted oncogenesis using an anti-Mullerian hormone promoter-SV40 oncogene construct, are of granulosa-c ell origin. Because tissue-specific, cell-surface molecules are of particul ar interest for the analysis and treatment of tumors, we examined the expre ssion of anti-Mullerian hormone type Il receptor in the ovaries of these tr ansgenic mice. We demonstrate that the anti-Mullerian hormone type II recep tor is expressed not only in normal ovarian follicles, but also in granulos a cell tumors. Using a cell line derived from one of these tumors, we show that the anti-Mullerian hormone type II receptor protein is present on the surface of tumor cells and binds anti-Mullerian hormone. Furthermore, we sh ow that the anti-Mullerian hormone receptor is functional in the granulosa tumor cell line, with anti-Mullerian hormone treatment inducing selective a ctivation of Smad1. In conclusion, in this study we present a new murine tr ansgenic model of granulosa cell tumors of the ovary and, using this model, we demonstrate for the first time cell-surface expression of a highly tiss ue-specific molecule, anti-Mullerian hormone type II receptor, as well as t he selective activation of Smad proteins by anti-Mullerian hormone, in gran ulosa tumor cells.