HORMONAL-REGULATION OF PROLIFERATION AND TRANSFORMING GROWTH-FACTORS GENE-EXPRESSION IN HUMAN ENDOMETRIAL ADENOCARCINOMA XENOGRAFTS

We have previously shown that estrogen and progestins regulate both ce llular proliferation and transforming growth factor (TGF) expression i n human endometrial adenocarcinoma cells in vitro. In the current stud y we examined the regulation of TGF-alpha and -beta(1) expression in e ndometrial adenocarcinoma xenografts. Four human endometrial adenocarc inoma cell lines were inoculated into female BALB/c nude mice. Adminis tration of 17 beta-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 effect s to E2 in animals carrying Ishikawa and HEC-1A cell xenografts but ha d no significant effect on growth of HEC-50 or HEC-1B xenografts. In i ntact mice inoculated with OH-Tam pellets and Ishikawa cells, the tumo rs were larger and had lower levels of TGF-alpha mRNA than in untreate d or E2 treated mice. In mice carrying Ishikawa, HEC-50 and HEC-1B cel l xenografts none of the hormones or agents tested altered TGF-beta(1) mRNA levels. In contrast, both E2 and OH-Tam significantly increased xenografts TGF-beta(1) mRNA levels in HEC-1A xenografts as well as sig nificantly reduced tumor size. Medroxyprogesterone acetate (MPA) had n o effect on tumor size of Ishikawa, HEC-1A and HEC-1B cell xenografts but significantly increased the size of HEC-50 xenografts. MPA signifi cantly reduced TGF-alpha expression in Ishikawa cell xenografts but ha d no effect in the other cell xenografts. MPA had no effect on TGF-bet a(1) expression in any of the xenografts. These observations demonstra te a discordance between the hormonal effects on TGF expression and ce llular proliferation and argue against a major role for the TGFs in re gulation of human endometrial adenocarcinoma cell proliferation in viv o.