ABSTRACT
Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of pancreatic ductal adenocarcinomas and may be predictor of treatment response. We determined if ATM deficiency renders pancreatic cancer cells more sensitive to fractionated radiation or commonly used chemotherapeutics. ATM expression was knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA. Isogenic cell lines were tested for sensitivity to several chemotherapeutic agents and radiation. DNA repair kinetics were analyzed in irradiated cells using the comet assay. We find that while rendering pancreatic cancer cells ATM-deficient did not significantly change their sensitivity to several chemotherapeutics, it did render them exquisitely sensitized to radiation. Pancreatic cancer ATM status may help predict response to radiotherapy.
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Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Funding
This work was supported by Susan Wojcicki and Dennis Troper, NIH grants (CA62924, R01CA176828 and U01CA210170), and the Rolfe Pancreatic Cancer Foundation. MG is the Sol Goldman Professor of Pancreatic Cancer Research.
Author contributions
MA performed experiments, generated and interpreted data; drafted and revised manuscript JRE provided expertize on radiosensitivity and chemosensitivity assays, interpreted data; revised manuscript 12 MG study concept and design; study supervision; interpretation of data; drafting and revision of manuscript; obtained funding.