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

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 38; no. 2; pp. 149 - 158
• Main Authors: López-González, José Sullivan, Aguilar-Cázares, Dolores, Prado-Garcı́a, Heriberto, Nieto-Rodrı́guez, Alejandro, Mandoki, Juan José, Avila-Moreno, Federico, Rivera, Rosa Marı́a, Chavarrı́a-Garcés, Jorge
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.11.2002; Elsevier Science
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - physiopathology; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - physiopathology; Carcinoma, Small Cell - genetics; Carcinoma, Small Cell - physiopathology; ELISA; Flow cytometry; Gene Expression Regulation, Neoplastic; Growth inhibition; Humans; Lung Neoplasms - genetics; Lung Neoplasms - physiopathology; Medical sciences; NSCLC cell lines; Phosphorylation; Pneumology; Receptors, Transforming Growth Factor beta - physiology; RNA messenger; RNA, Messenger - biosynthesis; RT-PCR; SCLC cell lines; TGF-β isoforms; TGF-β RII; Transforming Growth Factor beta - biosynthesis; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - pharmacology; Tumor Cells, Cultured; Tumors of the respiratory system and mediastinum; Flow cytometry; TGF-β RII; SCLC cell lines; RNA messenger; RT-PCR; TGF-β isoforms; NSCLC cell lines; Growth inhibition; ELISA; Human; Lung disease; Cell culture; Pathophysiology; Respiratory disease; Transforming growth factor; Cytokine; Exploration; Malignant tumor; Carcinogenesis; Bronchopulmonary; Polypeptide; Transforming growth factor β2; Bronchus disease; Growth factor; Non small cell carcinoma
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/S0169-5002(02)00177-0

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.