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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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Related in: MedlinePlus

Examples of MSP of DSC3 DNA from patients with primary CRC. M=methylated product; U=unmethylated product.
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fig5: Examples of MSP of DSC3 DNA from patients with primary CRC. M=methylated product; U=unmethylated product.

Mentions: The specificity of MSP in CRC cell lines encouraged us to analyse the methylation status of DSC3 DNA in 99 primary colorectal tumours by using the same primer pairs. Methylation of DSC3 DNA was detected in 41 out of 99 tumours (41.4%). Examples of MSP analysis in primary tumours are shown in Figure 5. Methylation of DSC3 DNA was found in 23 out of 39 (59%) patients who had a survival time <5 years, whereas in patients with survival time >5 years, only 30% of the patients (18 out of 60) harboured DSC3 DNA methylation, reaching statistical significance (P=0.004; Table 2). When we further analysed the effect of methylation on clinical outcome by Kaplan–Meier analysis, we found that tumours with methylated DSC3 DNA were significantly correlated to a worse clinical outcome than unmethylated tumours (P=0.002, Figure 6). However, the methylation status was not linked to any of clinical–pathological parameters including age, gender, size of tumour, tumour grading, and tumour stage in these patients.


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)

Examples of MSP of DSC3 DNA from patients with primary CRC. M=methylated product; U=unmethylated product.
© Copyright Policy
Related In: Results  -  Collection

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

fig5: Examples of MSP of DSC3 DNA from patients with primary CRC. M=methylated product; U=unmethylated product.
Mentions: The specificity of MSP in CRC cell lines encouraged us to analyse the methylation status of DSC3 DNA in 99 primary colorectal tumours by using the same primer pairs. Methylation of DSC3 DNA was detected in 41 out of 99 tumours (41.4%). Examples of MSP analysis in primary tumours are shown in Figure 5. Methylation of DSC3 DNA was found in 23 out of 39 (59%) patients who had a survival time <5 years, whereas in patients with survival time >5 years, only 30% of the patients (18 out of 60) harboured DSC3 DNA methylation, reaching statistical significance (P=0.004; Table 2). When we further analysed the effect of methylation on clinical outcome by Kaplan–Meier analysis, we found that tumours with methylated DSC3 DNA were significantly correlated to a worse clinical outcome than unmethylated tumours (P=0.002, Figure 6). However, the methylation status was not linked to any of clinical–pathological parameters including age, gender, size of tumour, tumour grading, and tumour stage in these patients.

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