DSC3 expression is regulated by p53, and methylation of DSC3 DNA is a prognostic marker in human colorectal cancer

Br J Cancer. 2011 Mar 15;104(6):1013-9. doi: 10.1038/bjc.2011.28. Epub 2011 Mar 1.


Background: Desmocollin 3 (DSC3), a member of the cadherin superfamily and integral component of desmosomes, is involved in carcinogenesis. However, the role of DSC3 in colorectal cancer (CRC) has not yet been established.

Methods: Desmocollin 3 expression in CRC cell lines was analysed by RT-PCR and western blotting. Methylation status of DSC3 was examined by demethylation tests, methylation-specific PCR, and bisulphite sequencing (BS). The regulatory role of p53 was investigated by transfection.

Results: Desmocollin 3 was downregulated in CRC cells at mRNA and protein levels. Desmocollin 3 expression was restored in five out of seven cell lines after 5-aza-2'-deoxycytidine (DAC) treatment. A heterogeneous methylation pattern was detected by BS in promoter region and exon 1 of DSC3. Methylation of DSC3 genomic sequences was found in 41% (41 out of 99) of primary CRC, being associated with poor prognosis (P=0.002). Transfection of p53 alone or in combination of DAC increased the DSC3 expression. Similarly, treatment with p53 inducer adriamycin alone or in combination with DAC enhanced DSC3 expression.

Conclusions: DNA methylation contributes to downregulation of DSC3 in CRC cell lines. Methylation status of DSC3 DNA is a prognostic marker for CRC. P53 appears to have an important role in regulating DSC3 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma / diagnosis
  • Carcinoma / genetics*
  • Cohort Studies
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics*
  • DNA Methylation*
  • Desmocollins / genetics*
  • Desmocollins / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Protein p53 / physiology*
  • Up-Regulation


  • Biomarkers, Tumor
  • DSC3 protein, human
  • Desmocollins
  • Tumor Suppressor Protein p53