ROLE OF TRANSFORMING GROWTH-FACTOR BETA-1 IN INDUCTION OF COLON-CARCINOMA DIFFERENTIATION BY HEXAMETHYLENE BISACETAMIDE

  • 15 January 1990
    • journal article
    • research article
    • Vol. 50  (2) , 261-265
Abstract
The differentiation agent hexamethylene bisacetamide (HMBA) increased expression of transforming growth factor .beta.1 (TGF.beta.1) 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 TGF.beta.2 or TGF.alpha. mRNA was observed. Both TGF.beta.1 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 TGF.beta.1 mimicked the growth-arresting effect on HMBA on three surgically resected moderately differentiated colon carcinomas in serum-free primary culture. Both TGF.beta.1 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 TGF.beta.1 mRNA by HMBA along with the parallel biological effects of HMBA and exogenously applied TGF.beta.1 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 TGF.beta.1.