Vascular Endothelial Growth Factor Expression Is Not Regulated by Estradiol or Medroxyprogesterone Acetate in Endometrial Carcinoma

Abstract

Objective: To determine whether the expression of vascular endothelial growth factor (VEGF) is altered by treatment of anin vivotumor with 17β-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 mice, from which it was serially passagedin vivo.The explanted tumor retained all the properties of the original tumor, including estrogen and 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 intramuscular administration of 2 mg MPA or weekly administrations of 2 mg MPA. Untreated tumor-bearing mice served as controls. The tumors were harvested 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 MPA, and expression was unaltered by continuous treatment with E2. Additional 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 doses of MPA did not alter expression at Weeks 1, 2, and 3. Conclusions: VEGF is constitutively expressed in thisin vivomodel of endometrial carcinoma, 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.