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Characterization of Transforming Growth Factor-ß-resistant Subclones Isolated from a Transforming Growth Factor-ß-sensitive Human Colon Carcinoma Cell Line¹

Bristol-Baylor Laboratory, Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030 [K. M. M., M. K. R., N. M. H., A. E. L., X. H. H., D. E. B.] and Department of Cellular and Molecular Biology, Preclinical AntiCancer, Bristol-Myers Company, Wallingford, Connecticut 06492 [M. G. B.]

Previous work indicated that transforming growth factor-ß (TGF-ß) 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-ß-sensitive parental line which were relatively refractory to the inhibitory effects of TGF-ß. While the parental cell line responded to TGF-ß 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-ß. 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-ß), inhibited the monolayer proliferation of both the parental cells and the TGF-ß-resistant sublines. Thus, the refractoriness observed in the isolated clones was relatively specific for TGF-ß.

¹ Supported by Grants CA34432 and CA45967 from the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 1/26/88. Revised 7/26/88. Revised 9/ 1/88. Accepted 9/13/88.