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

Cui T, Chen Y, Yang L, Knösel T, Zöller K, Huber O, Petersen I - Br. J. Cancer (2011)

Bottom Line: Methylation of DSC3 genomic sequences was found in 41% (41 out of 99) of primary CRC, being associated with poor prognosis (P=0.002).Methylation status of DSC3 DNA is a prognostic marker for CRC.P53 appears to have an important role in regulating DSC3 expression.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University Hospital Jena, Ziegelmühlenweg 1, Jena 07743, Germany.

ABSTRACT

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.

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DSC3 expression analysis in CRC cell lines. (A) Desmocollin 3 mRNA expression was analysed by real-time RT–PCR showing that DSC3 was downregulated in seven out of eight cancer cell lines. (B) In consistence with mRNA expression, western blotting revealed decreased DSC3 protein expression in CRC cell lines. Actin was used as loading control.
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fig1: DSC3 expression analysis in CRC cell lines. (A) Desmocollin 3 mRNA expression was analysed by real-time RT–PCR showing that DSC3 was downregulated in seven out of eight cancer cell lines. (B) In consistence with mRNA expression, western blotting revealed decreased DSC3 protein expression in CRC cell lines. Actin was used as loading control.

Mentions: We performed real-time RT–PCR to analyse the expression of DSC3 in eight colon cancer cell lines together with one normal colon cell line CCD-33Co. Compared with CCD-33Co, DSC3 mRNA expression was found downregulated in seven colon cancer cell lines, except Caco-2 (Figure 1A). Protein expression was analysed by western blotting showing decreased expression of DSC3 in cancer cell lines (Figure 1B).


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

Cui T, Chen Y, Yang L, Knösel T, Zöller K, Huber O, Petersen I - Br. J. Cancer (2011)

DSC3 expression analysis in CRC cell lines. (A) Desmocollin 3 mRNA expression was analysed by real-time RT–PCR showing that DSC3 was downregulated in seven out of eight cancer cell lines. (B) In consistence with mRNA expression, western blotting revealed decreased DSC3 protein expression in CRC cell lines. Actin was used as loading control.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3065270&req=5

fig1: DSC3 expression analysis in CRC cell lines. (A) Desmocollin 3 mRNA expression was analysed by real-time RT–PCR showing that DSC3 was downregulated in seven out of eight cancer cell lines. (B) In consistence with mRNA expression, western blotting revealed decreased DSC3 protein expression in CRC cell lines. Actin was used as loading control.
Mentions: We performed real-time RT–PCR to analyse the expression of DSC3 in eight colon cancer cell lines together with one normal colon cell line CCD-33Co. Compared with CCD-33Co, DSC3 mRNA expression was found downregulated in seven colon cancer cell lines, except Caco-2 (Figure 1A). Protein expression was analysed by western blotting showing decreased expression of DSC3 in cancer cell lines (Figure 1B).

Bottom Line: Methylation of DSC3 genomic sequences was found in 41% (41 out of 99) of primary CRC, being associated with poor prognosis (P=0.002).Methylation status of DSC3 DNA is a prognostic marker for CRC.P53 appears to have an important role in regulating DSC3 expression.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University Hospital Jena, Ziegelmühlenweg 1, Jena 07743, Germany.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus