Frequent inactivation of the transforming growth factor beta type II receptor in small-cell lung carcinoma cells.
Small-cell lung cancer (SCLC) has a significantly worse prognosis than other forms of bronchogenic carcinoma. Because transforming growth factor beta (TGF-beta) appears to play an important role in the pathogenesis of SCLC, we examined the status of the TGF-beta receptor system in a series of 11 human small-cell carcinoma cell lines. None of these cell lines expressed more than one-tenth the level of TGF-beta type II receptor (T beta R-II) gene mRNA produced by TGF-beta-sensitive normal epithelial cells. In addition, one of the cell lines expressed a second truncated T beta R-II transcript, which is predicted to encode a protein that lacks the terminal two-thirds of the serine-threonine kinase domain. No other structural alterations in the promoter or coding sequences of the T beta R-II gene were found in any of the cell lines, nor could the loss of T beta R-II mRNA expression be ascribed to de novo hypermethylation of promoter/enhancer sequences. These findings indicate that inactivation of the TGF-beta signaling pathway caused by the loss of T beta R-II gene expression is a common and, therefore, probably pathogenetically important feature of small-cell lung carcinoma.
de Jonge
R R
RR
Department of Medicine, Yale University School of Medicine, New Haven, CT 06520-8032, USA.
Garrigue-Antar
L
L
Vellucci
V F
VF
Reiss
M
M
D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D019175:DNA Methylation; D017931:DNA Primers; D004742:Enhancer Elements, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000096:biosynthesis; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II