A proapoptotic caspase recruitment domain protein gene, TMS1, is hypermethylated in human breast and gastric cancers

Anticancer Res. Nov-Dec 2002;22(6C):4163-8.


Background: Conway et al. demonstrated that methylation of the proapoptotic gene, TMS1, was observed in breast cancer cell lines and tissues, resulting in decreased TMS1 gene transcription. However, whether the TMS1 gene is hypermethylated in other cancers is uncertain.

Materials and methods: The expression of TMS1 mRNA was determined by quantitative RT-PCR. Methylation of the TMS1 gene was detected using methylation-specific PCR followed by bisulfite-modification of DNA.

Results: Methylation of the TMS1 gene was observed in breast, gastric and colorectal cancer cells. Down-regulation of TMS1 gene transcription in colorectal cancer cells was restored by treatment with a demethylating agent. Methylation of the TMS1 gene was observed in 2 out of 19 breast cancer specimens and 1 out of 9 gastric cancers, but in none of 13 colorectal cancers.

Conclusion: These results suggest a direct role for aberrant methylation of the TMS1 gene in the progression of breast and gastric cancer involving down-regulation of the proapoptotic TMS1 gene.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • CARD Signaling Adaptor Proteins
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Cytoskeletal Proteins
  • DNA Methylation*
  • Decitabine
  • Down-Regulation
  • Frozen Sections
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Protein Biosynthesis
  • Proteins / genetics*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Transcriptional Activation / drug effects
  • Tumor Cells, Cultured


  • CARD Signaling Adaptor Proteins
  • Cytoskeletal Proteins
  • PYCARD protein, human
  • Proteins
  • RNA, Messenger
  • Decitabine
  • Azacitidine