Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C1855645 (
KPC
)
1,473
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The Keap1-
Nrf2
system contributes to the maintenance of homeostasis by regulating oxidative stress responses in normal tissues and organs, and is exploited in various cancers for proliferation, survival and acquisition of therapy resistance. Pancreatic cancer remains one of the intractable cancers, despite the improved clinical outcomes of other types of cancer, due to its invasive and refractory nature to therapeutic intervention. The current study aimed to clarify the contribution of
Nrf2
to pancreatic carcinogenesis using a pancreas-specific mutant K-ras and p53 (
KPC
) mouse model. Deletion of
Nrf2
in
KPC
mice (KPCN) decreased the formation of precancerous lesions as well as the development of invasive pancreatic cancer. The pancreatic tumor-derived cancer cell lines from KPCN mouse showed decreased expression of glutathione S-transferases (GST), UDP glucuronosyltransferases (UGT) and ABC transporters. Along with these biochemical changes, cell lines from KPCN mice revealed increased sensitivity to oxidative stress and chemotherapeutic agent. The current study revealed that
Nrf2
contributes to pancreatic carcinogenesis in a way distinct from the chemoresistance of lung and esophagus, and that
Nrf2
could be a novel therapeutic target of pancreatic cancer.
...
PMID:Nrf2 promotes mutant K-ras/p53-driven pancreatic carcinogenesis. 2924 Aug 81
