Lack of correlation between growth inhibition by TGF-beta and the percentage of cells expressing type II TGF-beta receptor in human non-small cell lung carcinoma cell lines.
To determine the mechanisms involved in the evasion from TGF-beta 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-beta1 and TGF-beta2; (b) percentage of cells expressing TGF-beta RII; (c) responsiveness of the tumour cell lines to exogenous TGF-beta1 or TGF-beta2; and (d) presence of mRNA transcripts of the three TGF-beta isoforms and of the TGF-beta RII. Our results indicate that the SCLC cell lines do not synthesize the isoforms TGF-beta1 and TGF-beta2 nor the TGF-beta RII, thus avoiding inhibitory autocrine and paracrine TGF-beta actions. However, NSCLC cell lines express not only TGF-beta1, TGF-beta2 and TGF-beta RII mRNA transcripts, but also synthesize both isoforms and the TGF-beta RII. Although approximately 50% of the cells from the studied cell lines expressed the TGF-beta RII, different cell lines varied greatly in the sensitivity to the inhibitory action of TGF-beta. This could result from alterations in: (i) the structure of TGF-beta RII; (ii) the phosphorylation motif of TGF-beta RI; (iii) the molecules involved in the intracellular signalling pathway of TGF-beta; and (iv) cell cycle regulation.
López-González
José Sullivan
JS
Departamento de Enfermedades Crónico Degenerativas, Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, Col Sección XVI, Mexico DF 14080, Mexico. slopezgonzalez@yahoo.com
Aguilar-Cázares
Dolores
D
Prado-García
Heriberto
H
Nieto-Rodríguez
Alejandro
A
Mandoki
Juan José
JJ
Avila-Moreno
Federico
F
Rivera
Rosa María
RM
Chavarría-Garcés
Jorge
J
D000230:Adenocarcinoma / Q000235:genetics* / Q000503:physiopathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000503:physiopathology*; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000503:physiopathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta