ATM-deficiency increases genomic instability and metastatic potential in a mouse model of pancreatic cancer.

ABSTRACT: Germline mutations in ATM (encoding the DNA-damage signaling kinase, ataxia-telangiectasia-mutated) increase Familial Pancreatic Cancer (FPC) susceptibility, and ATM somatic mutations have been identified in resected human pancreatic tumors. Here we investigated how Atm contributes to pancreatic cancer by deleting this gene in a murine model of the disease expressing oncogenic Kras (Kras^G12D). We show that partial or total ATM deficiency cooperates with Kras^G12D to promote highly metastatic pancreatic cancer. We also reveal that ATM is activated in pancreatic precancerous lesions in the context of DNA damage and cell proliferation, and demonstrate that ATM deficiency leads to persistent DNA damage in both precancerous lesions and primary tumors. Using low passage cult

SUBMITTER: Drosos Y 

PROVIDER: S-EPMC5593966 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature