Estradiol and medroxyprogesterone acetate regulated genes in T47D breast cancer cells

Many mammary tumors express estrogen receptors (ER) and progesterone receptors (PR), and there is increasing evidence that progestins influence gene expression of breast tumor cells. To analyse the impact of progestins on breast cancer cells, we compared (a) the expression of two cytokines, involved in tumor progression, and searched (b) for differentially regulated genes by a microarray, containing 2400 genes, on T47D breast cancer cells cultured for 6 days with 17 beta-estradiol (E-2) or E-2 + medroxyprogesterone acetate (E-2 + MPA). Lower amounts of PDGF and TNF alpha were found in culture supernatants of E-2 + MPA treated T47D cells. MPA addition induced a 2.8-3.5-fold increase of the mRNA expression of (a) tristetraprolin, which is involved in the posttranscriptional regulation of cytokine biosynthesis, and (b) zinc-alpha 2-glycoprotein and Na, K-ATPase alpha 1-subunit, which both resemble differentiation markers of breast epithelium. In contrast, the mRNA expression of lipocalin 2, which promotes matrixmetalloproteinase-9 activity, was decreased five-fold in E-2 + MPA treated cells. Our data show that the expression of genes from various functional gene families is regulated differentially by E-2 and E-2 + MPA treatment in T47D cells. This suggests that exogenous progestins applied for therapy and endogenous changes of the progesterone levels during the menstrual cycle both influence breast cancer pathophysiology. (c) 2005 Elsevier Ireland Ltd. All rights reserved.