Unknown

Dataset Information

0

Inhibition of RAC1 GTPase sensitizes pancreatic cancer cells to ?-irradiation.


ABSTRACT: Radiation therapy is a staple treatment for pancreatic cancer. However, owing to the intrinsic radioresistance of pancreatic cancer cells, radiation therapy often fails to increase survival of pancreatic cancer patients. Radiation impedes cancer cells by inducing DNA damage, which can activate cell cycle checkpoints. Normal cells possess both a G1 and G2 checkpoint. However, cancer cells are often defective in G1 checkpoint due to mutations/alterations in key regulators of this checkpoint. Accordingly, our results show that normal pancreatic ductal cells respond to ionizing radiation (IR) with activation of both checkpoints whereas pancreatic cancer cells respond to IR with G2/M arrest only. Overexpression/hyperactivation of Rac1 GTPase is detected in the majority of pancreatic cancers. Rac1 plays important roles in survival and Ras-mediated transformation. Here, we show that Rac1 also plays a critical role in the response of pancreatic cancer cells to IR. Inhibition of Rac1 using specific inhibitor and dominant negative Rac1 mutant not only abrogates IR-induced G2 checkpoint activation, but also increases radiosensitivity of pancreatic cancer cells through induction of apoptosis. These results implicate Rac1 signaling in the survival of pancreatic cancer cells following IR, raising the possibility that this pathway contributes to the intrinsic radioresistance of pancreatic cancer.

SUBMITTER: Yan Y 

PROVIDER: S-EPMC4279370 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Inhibition of RAC1 GTPase sensitizes pancreatic cancer cells to γ-irradiation.

Yan Ying Y   Hein Ashley L AL   Etekpo Asserewou A   Burchett Katrina M KM   Lin Chi C   Enke Charles A CA   Batra Surinder K SK   Cowan Kenneth H KH   Ouellette Michel M MM  

Oncotarget 20141101 21


Radiation therapy is a staple treatment for pancreatic cancer. However, owing to the intrinsic radioresistance of pancreatic cancer cells, radiation therapy often fails to increase survival of pancreatic cancer patients. Radiation impedes cancer cells by inducing DNA damage, which can activate cell cycle checkpoints. Normal cells possess both a G1 and G2 checkpoint. However, cancer cells are often defective in G1 checkpoint due to mutations/alterations in key regulators of this checkpoint. Accor  ...[more]

Similar Datasets

| S-EPMC3446395 | biostudies-literature
| S-EPMC5440286 | biostudies-literature
2020-07-13 | PXD015284 | Pride
| S-EPMC5343905 | biostudies-other
| S-EPMC7918355 | biostudies-literature
| S-EPMC3400624 | biostudies-literature
| S-EPMC8338909 | biostudies-literature
| S-EPMC10814450 | biostudies-literature
| S-EPMC7923374 | biostudies-literature
| S-EPMC4747197 | biostudies-literature