Loss of transforming growth factor-β type II receptor gene expression in primary human esophageal cancer

Laure Garrigue-Antar, Rhonda F. Souza, Vincent F. Vellucci, Stephen J. Meltzer, Michael Reiss

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Cell lines derived from carcinomas of the upper aero-digestive tract are typically refractory to transforming growth factor β-mediated cell cycle arrest. Recently, we reported that the type II transforming growth factor β receptor (TβR-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 TβR-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 TβR-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 TβR-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 TβR-II mRNA. In this relatively small series of cases, loss of TβR-II expression was independent of pathologic tumor stage, histologic subtype, or outcome of patients with esophageal cancer. Thus, loss of expression of the TβR-II gene appears to be the predominant mechanism through which this gene is inactivated in esophageal cancer.

Original languageEnglish (US)
Pages (from-to)263-272
Number of pages10
JournalLaboratory Investigation
Volume75
Issue number2
StatePublished - Aug 1996

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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