TRANSFORMING GROWTH-FACTOR-BETA NEGATIVELY MODULATES PROLIFERATION AND C-FOS EXPRESSION OF THE HUMAN ENDOMETRIAL ADENOCARCINOMA CELL-LINE HEC-1-A

Growth factor regulation of normal and cancerous cell proliferation ha s been well-documented and may be mediated by protooncogene activity. The purpose of this study was to assess changes in proliferation and m itogen-induced c-fos mRNA expression of an endometrial carcinoma cell line, HEC-1-A, in response to TGF-beta, a potent growth-inhibitory pep tide. HEC-1-A cells were incubated in the presence or absence of TGF-b eta. Mitogen-stimulated cells were additionally treated with epidermal growth factor (EGF). Changes in proliferation were measured by [H-3]t hymidine uptake assays. Alterations in EGF-induced c-fos expression fo llowing TGF-beta pretreatment were assessed by Northern blot using a P -32-labeled human c-fos probe. Finally, chloramphenicol acetyltransfer ase assays were performed to evaluate c-fos promoter activity in respo nse to treatment conditions. Basal and EGF-stimulated proliferation wa s inhibited by TGF-beta in a dose- and time-dependent manner. TGF-beta also reversibly decreased EGF-induced c-fos mRNA expression in a dose - and time-dependent manner. Sequences in the c-fos promoter that were stimulated by EGF showed suppressed activity when preincubated with T GF-beta. These results show that TGF-P negatively modulates EGF-induce d c-fos expression, which may be related to the observed inhibition of carcinoma cell proliferation. (C) 1997 Academic Press.