Abstract
In this investigation we demonstrate expression of myc oncoproteins in HOC-7 ovarian adenocarcinoma cells. The cells were exposed to differentiation inducing agents such as dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), retinoic acid (RA) and transforming growth factor-beta 1 (TGF-beta 1). Myc protein expression in treated cells was then compared with that in control cultures and in monoclonal HOC-7 sublines, which are characterised by distinct phenotypes. Cells exposed to DMSO and DMF became markedly enlarged and flattened and developed cytoplasmic extensions. They looked similar to a subline, which revealed a less malignant and more differentiated cell phenotype. All four inducers prolonged the cell doubling time and reduced the saturation density to levels, normally found in the more differentiated subline. Furthermore, all inducers except RA elevated extracellular fibronectin, which is characteristic for less malignant epithelial cell phenotypes. All four agents inhibited myc oncoprotein expression reversibly (1% DMSO greater than 0.5% DMF greater than 10 microM RA greater than 10 ng ml-1 TGF-beta 1) and in time-dependent manner. Down-regulation of myc protein expression is, therefore, closely related to inducer-dependent growth reduction of HOC-7 cells and to the development of a less malignant cell phenotype.