Lack of correlation between growth inhibition by TGF-β and the percentage of cells expressing type II TGF-β receptor in human non-small cell lung carcinoma cell lines

Abstract

To determine the mechanisms involved in the evasion from TGF-β growth regulation in the small cell lung carcinoma (SCLC) cell lines and the non-small cell lung carcinoma (NSCLC) cell lines, we studied: (a) production of TGF-β1 and TGF-β2; (b) percentage of cells expressing TGF-β RII; (c) responsiveness of the tumour cell lines to exogenous TGF-β1 or TGF-β2; and (d) presence of mRNA transcripts of the three TGF-β isoforms and of the TGF-β RII. Our results indicate that the SCLC cell lines do not synthesize the isoforms TGF-β1 and TGF-β2 nor the TGF-β RII, thus avoiding inhibitory autocrine and paracrine TGF-β actions. However, NSCLC cell lines express not only TGF-β1, TGF-β2 and TGF-β RII mRNA transcripts, but also synthesize both isoforms and the TGF-β RII. Although approximately 50% of the cells from the studied cell lines expressed the TGF-β RII, different cell lines varied greatly in the sensitivity to the inhibitory action of TGF-β. This could result from alterations in: (i) the structure of TGF-β RII; (ii) the phosphorylation motif of TGF-β RI; (iii) the molecules involved in the intracellular signalling pathway of TGF-β; and (iv) cell cycle regulation.