Different signalling pathways involved in transforming growth factor-beta(1)-induced morphological change and type IV collagen synthesis in simian virus-40-immortalized normal human salivary gland duct and myoepithelial cell clones

To understand the specific cell type responsible for the synthesis of basement membrane components of the salivary gland, the effects of transforming growth factor (TGF)-beta(1) on morphological change, cellular proliferation and collagen synthesis were examined in these immortalized duct and myoepithelial cell clones, and the expression forms of their TGF-beta receptors analysed. When TGF-beta(1) was added to the cell clones in vitro, it induced a morphological alteration, with flattening in myoepithelial but not in duct cells. Although the growth of Mu1Lu mink lung epithelial cells was almost completely inhibited by TGF-beta(1), the duct and myoepithelial cells were partially resistant to such inhibition. By immunoblot analysis of immunoprecipitates, p53 was found bound to the simian virus-40 large T antigen, suggesting a functional loss of p53 in regulation of cell-cycle arrest. In the cloned myoepithelial cells but not the duct cells, TGF-beta(1) stimulated the production of type IV collagen. To attempt to understand the distinct responsiveness of cell clones to TGF-beta(1), the expression forms of TGF-beta receptors were examined by affinity cross-linking. Although the intensities of the cross-linked bands of the TGF-beta type II and type III receptors, particularly the type II, were weaker in the duct than the myoepithelial cell clones, the expression of the type II receptor mRNA was consistently detected in both clones. Accordingly, the reduction of TGF-beta(1) binding may have occurred at the post-transcriptional level. These findings imply that the cloned myoepithelial cells but not the cloned duct cells produce type IV collagen in response to TGF-beta(1) through the receptor-mediated signal transduction pathway, which is presumably disrupted in the cloned duct cells. Copyright (C) 1996 Elsevier Science Ltd.