CADM1/TSLC1 inactivation by promoter hypermethylation is a frequent event in colorectal carcinogenesis and correlates with late stages of the disease

Int J Cancer. 2011 Jan 15;128(2):266-73. doi: 10.1002/ijc.25356. Epub 2010 Mar 25.

Abstract

Cell adhesion molecule 1 (CADM1/TSLC1), a putative tumor suppressor involving in cell adhesion, proliferation and apoptosis, is frequently inactivated in several carcinomas due to promoter hypermethylation. But alterations of CADM1/TSLC1 in colorectal carcinogenesis and clinical significance have not been elucidated yet. The aim of this study was to determine the role of functional inactivation of CADM1/TSLC1 gene in colorectal tumorigenesis and its potential as a novel epigenetic marker for clinical assessment of patients with colorectal cancer. We measured CADM1/TSLC1 expression levels in 8 colorectal cancer cell lines, 54 primary colorectal carcinomas and their corresponding non-cancerous tissues by reverse transcription polymerase chain reaction, western blot analysis and immunohistochemistry. We analyzed CADM1/TSLC1 promoter methylation status by bisulfite genomic sequencing and the methylation special polymerase chain reaction, and evaluated its correlation with clinicopathological characteristics. All statistical tests were 2-sides. Downregulation of CADM1/TSLC1 expression was observed in 7 of 8 (88%) colorectal cancer cell lines and in 39 of 54 (72%) primary colorectal carcinomas. Hypermethylation of CADM1/TSLC1 promoter region occurred in 6 of 8 (75%) colorectal cancer cell lines and 32 of 54 (59%) primary colorectal carcinomas, and was correlated with advanced colorectal carcinoma. Epigenetic inactivation of CADM1/TSLC1 gene is a frequent alteration in development of colorectal cancer and can be a potential biomarker for molecular staging of patients with colorectal cancer.

MeSH terms

  • Adult
  • Aged
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / physiology
  • Cell Line, Tumor
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • DNA Methylation*
  • Down-Regulation
  • Female
  • Humans
  • Immunoglobulins / genetics*
  • Immunoglobulins / physiology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Promoter Regions, Genetic*
  • RNA, Messenger / analysis
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / physiology

Substances

  • CADM1 protein, human
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Immunoglobulins
  • RNA, Messenger
  • Tumor Suppressor Proteins