Sensitization of Human Pancreatic Cancer Cells Harboring Mutated K-ras to Apoptosis

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Sensitization of Human Pancreatic Cancer Cells Harboring Mutated K-ras to Apoptosis

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Title: Sensitization of Human Pancreatic Cancer Cells Harboring Mutated K-ras to Apoptosis
Author: Kim, Sung-Hoon; Ling, Shen; Chen, Chang-Yan

Note: Order does not necessarily reflect citation order of authors.

Citation: Shen, Ling, Sung-Hoon Kim, and Chang Yan Chen. 2012. Sensitization of human pancreatic cancer cells harboring mutated k-ras to apoptosis. PLoS ONE 7(7): e40435.
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Abstract: Pancreatic cancer is a devastating human malignancy and gain of functional mutations in K-ras oncogene is observed in 75%–90% of the patients. Studies have shown that oncogenic ras is not only able to promote cell growth or survival, but also apoptosis, depending upon circumstances. Using pancreatic cancer cell lines with or without expressing mutated K-ras, we demonstrated that the inhibition of endogenous PKC activity sensitized human pancreatic cancer cells (MIA and PANC-1) expressing mutated K-ras to apoptosis, which had no apoptotic effect on BxPC-3 pancreatic cancer cells that contain a normal Ras as well as human lung epithelial BAES-2B cells. In this apoptotic process, the level of ROS was increased and PUMA was upregulated in a p73-dependent fashion in MIA and PANC-1 cells. Subsequently, caspase-3 was cleaved. A full induction of apoptosis required the activation of both ROS- and p73-mediated pathways. The data suggest that PKC is a crucial factor that copes with aberrant K-ras to maintain the homeostasis of the pancreatic cancer cells harboring mutated K-ras. However, the suppression or loss of PKC disrupts the balance and initiates an apoptotic crisis, in which ROS and p73 appear the potential, key targets.
Published Version: doi:10.1371/journal.pone.0040435
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405084/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10445633
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