We have examined the expression of the p53 and Rb-1 tumor-suppressor genes in seven human pancreatic carcinoma cell lines and 10 primary pancreatic carcinomas.
Coexistent inactivations of both MTS1 and p53 was common and suggests that abnormal regulation of cyclin-dependent kinases may play an important role in the biology of pancreatic carcinoma.
Both failed to specifically suppress p53 protein production in a cell-free assay system or to have any effect on mutant p53 expression by human pancreatic cancer cell lines.
Although the rate of p53 mutations in pancreatic tumours is of the same order as in other adenocarcinomas (> or = 50%), an antibody response was found in only 5/78 (6.4%) sera from patients with pancreatic cancer.
These data support a role for p53 gene alterations in human pancreatic cancer, and suggest that loss of its regulatory functions may constitute one of the differences between pancreatic cancer and chronic pancreatitis.
We investigated the therapeutic benefits of p53 expression by the transduction of wild-type p53 gene into p53-null human pancreatic carcinoma cells (AsPC-1).
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.
In this study, the authors demonstrate that p53 positive cells precisely reflect its gene mutations, and also establish systematic procedures for the preoperative diagnosis of patients with pancreatic carcinoma.
The consequences of stable reintroduction of wt p53 on apoptosis and differentiation was examined in a poorly differentiated pancreatic carcinoma cell line (Panc-1), possessing only mutant (mt) p53 (codon 273 mutation).
On examination of DNA from dewaxed sections of the tumor, we found no p53 mutation in the tumor tissue, but found two K-ras mutations in codon 12; this pattern of mutation commonly occurs in pancreatic carcinoma, indicating a somewhat genetic relationship of OGTP to pancreatic carcinoma.
This study confirms that loss of chromosomes, particularly chromosomes 17 and 18, which carry the p53 and DCC genes, are common in pancreas cancer.Chromosome 20 is also frequently lost.
The p16(INK4a) (MTS-1, CDKN2) gene product acts in the same pathway as p53 to inhibit cell cycle progression at G1/S. p16(INK4a) is deleted and/or mutated in a significant fraction of human tumors, including pancreatic carcinoma.