Expression of proteins in p53 (p14ARF-mdm2-p53-p21WAF/CIP1) pathway and their significance in exocrine pancreatic carcinoma.
- Author:
Guan-zhen YU
1
;
Ming-hua ZHU
;
Can-rong NI
;
Fang-mei LI
;
Jian-ming ZHENG
;
Zhi-jin GONG
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Age Factors; Apoptosis; Cell Cycle; Cell Cycle Proteins; metabolism; Cyclin-Dependent Kinase Inhibitor p21; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Nuclear Proteins; metabolism; Pancreatic Neoplasms; metabolism; pathology; Proto-Oncogene Proteins; metabolism; Proto-Oncogene Proteins c-mdm2; Tumor Suppressor Protein p14ARF; metabolism; Tumor Suppressor Protein p53; metabolism
- From: Chinese Journal of Pathology 2004;33(2):130-134
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the expression of p14(ARF), p53, mdm2 and p21(WAF/CIP1) proteins and their relationship in exocrine pancreatic carcinoma.
METHODSSpecimens of pancreatic carcinoma, adjacent non-neoplastic pancreatic tissue and pancreatic benign lesions were examined for p14(ARF), p53, mdm2 and p21(WAF/CIP1) protein expression by tissue microarray technique and immunohistochemistry.
RESULTSThe expression of p14(ARF), p53, mdm2 and p21(WAF/CIP1) proteins in pancreatic carcinoma were 35.3% (59/167), 57.5% (96/101), 64.1% (107/167) and 39.5% (66/167) respectively. The expression of p53 proteins was increased in pancreatic carcinoma (P < 0.01), while the expression of p14(ARF) and p21(WAF/CIP1) proteins was reduced (P < 0.05), as compared with that in non-neoplastic pancreatic tissue. p21(WAF/CIP1) protein expression in pancreatic carcinoma significantly correlated with the age of patients and perineural invasion (P < 0.05). p53 protein expression correlated significantly with tumor differentiation, lymph node metastasis and perineural invasion (P < 0.05). Mdm2 protein expression correlated significantly with tumor differentiation (P < 0.05), while p14(ARF) protein expression correlated significantly with the age of patients and metastasis (P < 0.05). There was also statistic correlation between the expression of these four genes (P < 0.05).
CONCLUSIONSOverexpression of p53 and mdm2 and loss of p14(ARF) and p21(WAF/CIP1) expression may contribute to the pathogenesis of pancreatic carcinoma. These proteins play a critical role in cell cycle arrest and apoptosis after DNA damage through p14(ARF)-mdm2-p53-p21(WAF/CIP1) pathway. Detection of p53 and Mdm2 protein overexpression may be useful in evaluation of the aggressiveness of pancreatic carcinoma.
