VASCULAR ENDOTHELIAL GROWTH-FACTOR EXPRESSION IS NOT REGULATED BY ESTRADIOL OR MEDROXYPROGESTERONE ACETATE IN ENDOMETRIAL CARCINOMA

Objective: To determine whether the expression of vascular endothelial growth factor (VEGF) is altered by treatment of an in vivo tumor with 17 beta-estradiol (E2) or medroxyprogesterone acetate (MPA). Methods: A well-differentiated endometrial carcinoma tumor was isolated from a patient and explanted into the dorsal skin of ovariectomized nude mic e, from which it was serially passaged in vivo. The explanted tumor re tained all the properties of the original tumor, including estrogen an d progesterone receptor expression and growth promotion and inhibition by E2 and MPA, respectively. The mice were treated with continuous E2 administration followed by treatment with either a single intramuscul ar administration of 2 mg MPA or weekly administrations of 2 mg MPA. U ntreated tumor-bearing mice served as controls. The tumors were harves ted at 0 to 21 days from first MPA administration. RNA from the tumors was isolated and VEGF expression was determined by Northern analysis. Results: VEGF was expressed in the absence of treatment with E2 or MP A, and expression was unaltered by continuous treatment with E2. Addit ional treatment with a single dose of MPA did not alter expression at Days 1, 2, 3, 7, 14, and 21, and additional treatment with weekly dose s of MPA did not alter expression at Weeks 1, 2, and 3. Conclusions: V EGF is constitutively expressed in this in vivo model of endometrial c arcinoma, and its expression is unaltered by treatment with E2 or E2 MPA. Regulation of VEGF expression is not a mechanism by which these hormones exert their growth effects on endometrial tumors. (C) 1996 Ac ademic Press, Inc.