Characterization of transforming growth factor-β-resistant subclones isolated from a transforming growth factor-β-sensitive human colon carcinoma cell line

Previous work indicated that transforming growth factor-beta (TGF-beta) elicits proliferation-inhibitory effects in the human colon carcinoma cell line MOSER. This paper describes the isolation and characterization of spontaneously arising subclones from this TGF-beta-sensitive parental line which were relatively refractory to the inhibitory effects of TGF-beta. While the parental cell line responded to TGF-beta with an inhibition of cellular proliferation in monolayer culture and in soft agarose, an increase in extracellular fibronectin, and a down-regulation of c-myc protooncogene expression, these responses were absent or attenuated in the sublines. However, the resistant clones retained the ability to specifically bind TGF-beta. N,N-Dimethylformamide and retinoic acid, two other agents associated with induction of a partial differentiation-like response in the MOSER parental cells (similar to that elicited by TGF-beta), inhibited the monolayer proliferation of both the parental cells and the TGF-beta-resistant sublines. Thus, the refractoriness observed in the isolated clones was relatively specific for TGF-beta.