Abstract:
:Pancreatic cancer remains a highly lethal malignancy. We have recently shown that simultaneous expression of Kras and mutant Tp53R175H promotes invasive ductal adenocarcinoma from pancreatic ductal cells. We hypothesized specific mutations in TP53 have divergent mechanisms of transforming ductal cells. In order to understand the role of mutant TP53 in transforming pancreatic ductal cells, we used a lentiviral system to express mutant TP53R175H and TP53R273H, two of the most frequently mutated TP53 alleles in pancreatic cancer patients, in immortalized, but not transformed, pancreatic ductal epithelial cells carrying a KRAS mutation (HPNE:KRASG12D). Mutant TP53 expression enhanced colony formation and an RPPA assay results revealed TP53R175H uniquely induced HSP70 expression in HPNE:KRASG12D cells. In the context of TP53R175H expression; we observed nuclear localization of HSP70. We performed immunoprecipitation experiments to show mutant p53R175H binds to HSP70. We also provide evidence mutant p53R175H is important for HSP70 stability and, more importantly, HSP70 is required for mutant p53 stability. These data are critical in the context of events leading to cellular transformation in the pancreas.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Polireddy K,Singh K,Pruski M,Jones NC,Manisundaram NV,Ponnela P,Ouellette M,Van Buren G,Younes M,Bynon JS,Dar WA,Bailey JMdoi
10.1016/j.canlet.2019.03.047subject
Has Abstractpub_date
2019-07-01 00:00:00pages
122-130eissn
0304-3835issn
1872-7980pii
S0304-3835(19)30211-3journal_volume
453pub_type
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