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

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. Desmocollin 3 expression in CRC cell lines was analysed by RT-PCR and western blotting. M...

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Bibliographic Details
Published in:British journal of cancer 2011-03, Vol.104 (6), p.1013-1019
Main Authors: CUI, T, CHEN, Y, YANG, L, KNÖSEL, T, ZÖLLER, K, HUBER, O, PETERSEN, I
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biological and medical sciences
Biomarkers, Tumor - analysis
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Cancer research
Carcinoma - diagnosis
Carcinoma - genetics
Cell cycle
Cohort Studies
Colorectal cancer
Colorectal Neoplasms - diagnosis
Colorectal Neoplasms - genetics
Desmocollins - genetics
Desmocollins - metabolism
DNA Methylation
Female
Gastroenterology. Liver. Pancreas. Abdomen
Gene Expression Regulation, Neoplastic
Genes
Humans
Male
Medical prognosis
Medical research
Medical sciences
Middle Aged
Molecular Diagnostics
Prognosis
Proteins
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumor Suppressor Protein p53 - metabolism
Tumor Suppressor Protein p53 - physiology
Tumors
Up-Regulation
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Summary: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. 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. 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. 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.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2011.28