title: Reduced levels of p15INK4b, p16INK4a, p21cip1 and p27kip1 in pancreatic             carcinoma.
abstract: Pancreatic carcinoma is one of the leading causes of cancer mortality worldwide,             although the molecular mechanisms of this disease are poorly understood. The aim             of this study was to examine the expression of cyclin-dependent kinase inhibitors             (CDKIs) and the epigenetic modifications in the promoters of these genes. We also             evaluated the correlation between the methylation status of CDKI genes and smoking             habit in clinical pancreatic carcinoma specimens. Western blotting and real-time             PCR were performed to assess CDKI expression. Methylation-specific PCR was carried             out to examine the methylation status of the promoters of CDKI genes. In this             study, we revealed that reduced levels of the CDKI proteins, p15INK4b, p16INK4a,             p21cip1 and p27kip1, are a prominent feature of pancreatic carcinoma patients.             The DNA hypermethylation of the promoter was observed in 40% (2 of 5) of the p15INK4b             genes, 60% (3 of 5) of the p16INK4a genes and 60% of the p21cip1 genes, which             markedly correlated with their decreased mRNA expression. No hypermethylation             was detected in the p27kip1 gene promoter in 5 pancreatic carcinoma patients with             markedly decreased expression of p27kip1 mRNA, suggesting an alternative mechanism             of p27kip in these patients. In this study, patients with a smoking habit displayed             methylation of 2 CDKI genes in their pancreatic carcinoma specimens. We concluded             that epigenetic modification via hypermethylation represents a critical mechanism             for the inactivation of CDKI genes in pancreatic carcinoma.
authors.affiliation: The Third General Surgery Department, Zhanghai Hospital, Second Military Medical University, Shanghai, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ji
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: JingQi
authors.initials: J
authors.lastname: Li
authors.forename: YingQi
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D012907:Smoking
chemical_list: C493956:CDKN1A protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27