Loss of transforming growth factor-beta type II receptor gene expression in primary human esophageal cancer.
Cell lines derived from carcinomas of the upper aero-digestive tract are typically refractory to transforming growth factor beta-mediated cell cycle arrest. Recently, we reported that the type II transforming growth factor beta receptor (T beta R-II) gene can be inactivated on the basis of missense mutations in such cell lines. These findings prompted us to investigate the molecular status of the T beta R-II gene in primary tumor specimens. Among 21 of 24 evaluable primary esophageal carcinomas, there were 6 cases (28.5%; 95% confidence interval, 11% to 52%) in which T beta R-II transcripts were low or undetectable by a reverse transcription PCR assay. In one of these cases, we were able to ascribe the loss of T beta R-II gene expression to high-density methylation of promoter sequences. We failed to detect any mutations within the open reading frame of the remaining tumors that expressed T beta R-II mRNA. In this relatively small series of cases, loss of T beta R-II expression was independent of pathologic tumor stage, histologic subtype, or outcome of patients with esophageal cancer. Thus, loss of expression of the T beta R-II gene appears to be the predominant mechanism through which this gene is inactivated in esophageal cancer.
Garrigue-Antar
L
L
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8032, USA.
Souza
R F
RF
Vellucci
V F
VF
Meltzer
S J
SJ
Reiss
M
M
D001483:Base Sequence; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II