M. Dutertre et al., Ovarian granulosa cell tumors express a functional membrane receptor for anti-Mullerian hormone in transgenic mice, ENDOCRINOL, 142(9), 2001, pp. 4040-4046
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.