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

Lab Invest. 1996 Aug;75(2):263-72.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Carcinoma / chemistry
  • Carcinoma / genetics*
  • Esophageal Neoplasms / chemistry
  • Esophageal Neoplasms / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Molecular Sequence Data
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / genetics*

Substances

  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II