Collectively, these findings reveal a highly dynamic and interdependent metabolic, transcriptional, and epigenetic regulatory network governed by Yap, Myc, Sox2, and p53 that dictates pancreatic tumor metabolism, growth, survival, and differentiation.
Supernumerary and abnormal centrosomes are observed in the earliest stages of pancreatic tumor development, and the p53 pathway acts as an initial barrier to the proliferation of cells with extra centrosomes.
Stat3, Il6st (encodes gp130), or Trp53 were disrupted, or a mutant form of P53 (P53R172H) or transgenic sgp130 were expressed, in mice that developed pancreatic tumors resulting from expression of activated KRAS (KrasG12D, KC mice).
Owing to the high incidence of p53 mutations in PanIN 3 lesions and pancreatic tumors, we interrogated the comparative ability of adult pancreatic acinar and ductal cells to respond to oncogenic Kras and mutant Tp53(R172H) using Hnf1b:CreER(T2) and Mist1:CreER(T2) mice.
Collectively, our results show that decreased MGMT expression is correlated with p53 activation, and significantly reduced primary pancreatic tumor growth.
This study was undertaken to evaluate the impact of wild-type or mutant p53 status on the synergistic effects of 5-Fluorouracil (5-FU) and radiation (XRT) in pancreatic tumors.
Gene therapy approaches involving p53 replacement are promising due to the central role of p53 in the cellular response to DNA damage and the high incidence of p53 mutations in pancreatic tumors.
Reduced expression of p53 and cyclin A in intraductal mucin-hypersecreting neoplasm of the pancreas compared with usual pancreatic ductal adenocarcinoma.
Treatment of nude mice with the retroviral p53 vector resulted in a significant inhibition of growth of the primary pancreatic tumor, as well as the peritoneal tumor deposits, compared with the LXSN control vector.
With the aid of a newly developed target unmasking fluid (TUF), p53 overexpression was visualized by immunohistochemistry on recent and archival paraffin-embedded tissue samples of colon, stomach, and pancreas neoplasms.