Nuclear accumulation of p53 correlates significantly with clinical features and inversely with the expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in pancreatic cancer.
Recent studies have suggested a p53-independent expression of p21(WAF1/CIP1). We investigated the correlation between p53 overexpression and the expression of p21(WAF1/CIP1) in 57 patients with pancreatic adenocarcinoma. By means of reverse transcription and polymerase chain reaction (RT-PCR), we examined the mRNA levels of WAF1/CIP1 and compared them with the p53 status in 20 patients and in a further six pancreatic tumour cell lines. In pancreatic cancer tissues, immunohistological evaluation revealed a significant correlation between active p53 and p21(WAF1/CIP1) (P < 0.005) as well as WAF1/CIP1 mRNA expression (P < 0.005). This coherence was also evident in human pancreatic carcinoma cell lines. The analysis of p53 and p21(WAF1/CIP1) expression in relation to clinicopathological features revealed a significant correlation between p53 overexpression and tumour stage, tumour size, grading and lymph node metastases, whereas p21(WAF1/CIP1) expression correlated only with tumour size. We conclude that the expression of p21(WAF1/CIP1) normally depends on active p53, but that there may also exist p53-independent pathways of induction that reduce the correlation of p21(WAF1/CIP1) to clinicopathological features.
Harada
N
N
Department of General Surgery, University of Ulm, Germany.
Gansauge
S
S
Gansauge
F
F
Gause
H
H
Shimoyama
S
S
Imaizumi
T
T
Mattfeld
T
T
Schoenberg
M H
MH
Beger
H G
HG
D000328:Adult; D000368:Aged; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53