The differentiation agent hexamethylene bisacetamide (HMBA) increased expression of transforming growth factor β1 (TGFβ1) mRNA in HT29 colon carcinoma cells. The increase was evident after 24 h and was maintained at levels 4–5-fold the control levels for at least 5–13 days. No increase in expression of TGFβ2 or TGFα mRNA was observed. Both TGFβ1 and HMBA induced loss of expression of a cell surface malignancy marker on HT29 cells, and both decreased cell growth in serum-free medium. Exogenously applied TGFβ1 mimicked the growth-arresting effect of HMBA on three surgically resected moderately differentiated colon carcinomas in serum-free primary culture. Both TGFβ1 and HMBA increased the tumor growth fraction in a second group of three more aggressive colon carcinomas, while neither agent had any measurable growth-modulating activity on two other colon carcinomas. The induction of TGFβ1 mRNA by HMBA along with the parallel biological effects of HMBA and exogenously applied TGFβ1 on resected carcinomas and on HT29 cells suggest that the effects of HMBA on colon carcinoma cells may be mediated in part by induction of TGFβ1.

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Supported by CA45783 to E. F., by a National Cancer Institute fellowship to P. S., and by CA46413 and Veterans Administration support to R. J. C.

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