Format

Send to

Choose Destination
Life Sci. 2011 Jun 6;88(23-24):1063-9. doi: 10.1016/j.lfs.2011.03.021. Epub 2011 Apr 2.

Expression of KL-6/MUC1 in pancreatic ductal carcinoma and its potential relationship with β-catenin in tumor progression.

Author information

1
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Japan.

Abstract

AIM:

The aim of this study was to evaluate the expression of Krebs yon den Lundgen-6/Mucin 1 (KL-6/MUC1) in pancreatic ductal carcinoma and its potential relationship with β-catenin in tumor progression.

MAIN METHODS:

The expressions of KL-6/MUC1 and β-catenin in 18 cases of pancreatic ductal carcinoma were detected by immunohistochemical staining. To determine the impact of KL-6/MUC1 down-regulation on pancreatic ductal carcinoma progression, siRNA targeting MUC1 was used to knockdown KL-6/MUC1 expression. The down-regulation of KL-6/MUC1 expression was confirmed by reverse transcription-polymerase chain reaction and immunofluorescence staining. E-cadherin and E-cadherin/β-catenin complex expressions were determined by immunoprecipitation. The expressions of KL-6/MUC1, β-catenin, cyclin D1 and c-myc were detected by Western blot. Cell proliferation, apoptosis and invasive abilities were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay, Annexin V-FITC apoptosis detection kit and invasion assay.

KEY FINDINGS:

Positive KL-6/MUC1 staining was observed in the cancer tissues of all the 18 pancreatic ductal carcinoma cases (100.0%), and high nuclear β-catenin expression was seen in 12 cancers (66.7%). Reverse transcription-polymerase chain reaction and immunofluorescence staining showed that both KL-6/MUC1 mRNA and protein were effectively silenced by MUC1 siRNA. After KL-6/MUC1 knockdown, E-cadherin and E-cadherin/β-catenin complex expressions were increased, while the nuclear β-catenin, cyclin D1, and c-myc expressions were decreased. Down-regulation of KL-6/MUC1 also resulted in slower proliferation, increased apoptosis and decreased invasive ability.

SIGNIFICANCE:

This study indicated that KL-6/MUC1 played a complex role in regulating pancreatic ductal carcinoma cell proliferation, apoptosis, and invasion, and also supported the hypothesis that there is a functional link between KL-6/MUC1 expression and β-catenin subcellular localization.

PMID:
21466814
DOI:
10.1016/j.lfs.2011.03.021
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center