Effects of transforming growth factors and regulation of their mRNA levels in two human endometrial adenocarcinoma cell lines

Abstract

The effects of the transforming growth factor-β1 (TGF-β1) and epidermal growth factor (EGF) on the growth of cells from 2 endometrial cancer lines, Ishikawa and HEC-50 were evaluated by measuring rates of DNA synthesis and changes in cell numbers during culture. EGF at 17 and 1.7 nM concentrations consistently enhanced HEC-50 cell proliferation. TGF-β1 inhibited Ishikawa cell proliferation but, unexpectedly for epithelium-derived cells, stimulated HEC-50 cell growth. This effect of interest as it indicates that endometrial cells can acquire an altered responsiveness to a growth inhibitor during the process of malignant transformation. Northern blot analyses showed expression of TGF-α, TGF-β1 and EGF receptors mRNA in both cell lines. Neither estradiol (E 2) nor 4-hydroxytamoxifen (OHTam) affected mRNA levels for either TGF-α or TGF-β in HEC-50 cells, a line unresponsive to E 2 proliferation. In Ishikawa cells, previously shown to respond to both E 2 and OHTam by increasing proliferation rates, E 2 increased TGF-α mRNA and reduced TGF-β mRNA levels. OHTam lowered the levels of both mRNA species, although the effect was greater on TGF-β than TGF-α mRNA. These data are consistent with, but do not prove, the existence of a possible autocrine regulation by TGF-α and TGF-β of human cancer cell proliferation, which might be under E 2 influence in Ishikawa cells.