Hormonal regulation of proliferation and transforming growth factors gene expression in human endometrial adenocarcinoma xenografts

Abstract

We have previously shown that estrogen and progestins regulate both cellular proliferation and transforming growth factor (TGF) expression in human endometrial adenocarcinoma cells in vitro. In the current study we examined the regulation of TGF-α and - β 1 expression in endometrial adenocarcinoma xenografts. Four human endometrial adenocarcinoma cell lines were inoculated into female BALB/c nude mice. Administration of 17β-estradiol (E2) increased tumor size in intact mice inoculated with Ishikawa, HEC-50 and HEC-1B cells but inhibited growth of HEC-1A xenografts. 4-Hydroxy tamoxifen (OH-Tam) had similar effects to E2 in animals carrying Ishikawa and HEC-1A cell xenografts but had no significant effect on growth of HEC-50 or HEC-1B xenografts. In intact mice inoculated with OH-Tam pellets and Ishikawa cells, the tumors were larger and had lower levels of TGF-α mRNA than in untreated or E2 treated mice. In mice carrying Ishikawa, HEC-50 and HEC-1B cell xenografts none of the hormones or agents tested altered TGF- β 1 mRNA levels. In contrast, both E2 and OH-Tam significantly increased xenografts TGF- β 1 mRNA levels in HEC-1A xenografts as well as significantly reduced tumor size. Medroxyprogesterone acetate (MPA) had no effect on tumor size of Ishikawa, HEC-1A and HEC-1B cell xenografts but significantly increased the size of HEC-50 xenografts. MPA significantly reduced TGF-α expression in Ishikawa cell xenografts but had no effect in the other cell xenografts. MPA had no effect on TGF- β 1 expression in any of the xenografts. These observations demonstrate a discordance between the hormonal effects on TGF expression and cellular proliferation and argue against a major role for the TGFs in regulation of human endometrial adenocarcinoma cell proliferation in vivo.