Infrequently methylated event at sites -362 to -142 in the promoter of TGF beta R1 gene in non-small cell lung cancer

J Cancer Res Clin Oncol. 2008 Aug;134(8):919-25. doi: 10.1007/s00432-008-0392-4. Epub 2008 Apr 18.

Abstract

Introduction: Many malignant tumor cells, including non-small cell lung cancer (NSCLC) cells, are frequently resistant to transforming growth factor beta (TGF-beta)-mediated signal transduction. This refractory response might be due to reduced/loss expression of the TGF-beta receptor 1 (TGF beta R1). However, little was known about connection between inactivation of the TGF beta R1 gene and the presence of CpG methylated promoter in NSCLC.

Materials and methods: To investigate whether, there is an epigenetic mechanism underlying inactivation of TGF beta R1 in NSCLC, we performed the immunohistochemical and DNA methylation analyzes of TGF beta R1 in tumor and the paired normal tissues from 35 resection specimens.

Conclusion: As the first report, the present study demonstrated loss or reduction of TGF beta R1 expression in 11 (31.4%) of 35 NSCLC tissues, suggesting that reduced TGF beta R1 expression could contribute to the development of malignant phenotype of NSCLC, even if no aberrant DNA methylated site was found at sites -362 to -142 of TGF beta R1 promoter region under investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA Methylation*
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / genetics
  • Protein Serine-Threonine Kinases / genetics*
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / genetics*

Substances

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