Modulation of differentiation and proliferation in human colon carcinoma cells by transforming growth factor β1 and β2

Abstract

We have previously characterized the diversity of cellular responses to transforming growth factor (TGF)-beta 1 from human colon carcinoma cells. We now show that morphological alteration and part of the growth-inhibitory responses elicited by growth factor (GF) are associated with the secondary effect of the induction of synthesis of extracellular matrix (ECM) glycoproteins. Specifically, morphological alteration is associated with the ECM glycoprotein laminin, and growth inhibition is associated with both laminin and fibronectin. Both TGF-beta 1 and TGF-beta 2 down-modulate the expression of nucleolar protein B23 (also known as numatrin or nucleophosmin, a positive regulator of cell proliferation). With one exception, the biological effects of both TGF-beta 1 and TGF-beta 2 on these human colon carcinoma cell lines are identical. Both GFs up-modulate the expression of carcinoembryonic antigen (CEA) and CEA-related gene products. However, some of these products are differentially regulated by TGF-beta 1 and TGF-beta 2. The differences in the profile of the induction of these CEA and CEA-related gene products, in the responsive cells, functionally distinguish TGF-beta 1 from TGF-beta 2. Finally, we identified and characterized some of the cellular proteins, the expression of which is up-modulated by GF. These proteins are epithelium-associated, differentiation-related cytokeratins. Both TGF-beta 1 and TGF-beta 2 up-modulate expression of the acidic and basic subtypes of human keratins in the responsive human colon carcinoma cells. Both the responsive and unresponsive cells, however, possess receptors for GFs.