Journal
BRITISH JOURNAL OF CANCER
Volume 104, Issue 6, Pages 1013-1019Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2011.28
Keywords
DSC3; DNA methylation; p53; prognosis; colorectal cancer
Categories
Funding
- Deutsche Krebshilfe [108003]
Ask authors/readers for more resources
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-20-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. British Journal of Cancer (2011) 104, 1013-1019. doi: 10.1038/bjc.2011.28 www.bjcancer.com
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available