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Pim-3 contributes to radioresistance through regulation of the cell cycle and DNA damage repair in pancreatic cancer cells.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2016 Apr 22; Vol. 473 (1), pp. 296-302. Date of Electronic Publication: 2016 Mar 22. - Publication Year :
- 2016
-
Abstract
- Resistance of cancer cells to chemoradiotherapy is a major clinical problem in pancreatic cancer treatment. Therefore, understanding the molecular basis of cellular resistance and identifying novel targets are essential for improving treatment efficacy for pancreatic cancer patients. Previous studies have demonstrated a significant role for Pim-3 in pancreatic cancer survival against gemcitabine-induced genotoxic stress. Here, we observed that radiation treatment enhanced Pim-3 expression in human pancreatic cancer cells in vitro. Stable overexpression of Pim-3 in pancreatic cancer cells significantly protected cells against radiation treatment by attenuating G2/M phase cell cycle arrest and DNA damage response. Silencing of Pim-3 expression significantly elevated the phosphorylation of histone variant H2AX, a marker of DNA double strand breaks, and decreased the activation of ataxia-telangiectasia-mutated (ATM) kinase, along with its downstream targets, eventually enhancing the radiosensitivity of human pancreatic cancer cells in vitro and in vivo. Hence, we demonstrated a novel function for Pim-3 in human pancreatic cancer cell survival against radiation. Targeting Pim-3 may be a promising way to improve treatment efficacy in combination with radiotherapy in human pancreatic cancer.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Ataxia Telangiectasia Mutated Proteins metabolism
Cell Cycle
Cell Line, Tumor
Cell Survival
DNA Breaks, Double-Stranded
Female
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Pancreatic Neoplasms pathology
Phosphorylation
Radiation, Ionizing
DNA Damage
DNA Repair
Gene Expression Regulation, Neoplastic
Pancreatic Neoplasms metabolism
Pancreatic Neoplasms radiotherapy
Protein Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins metabolism
Radiation Tolerance genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 473
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 27016481
- Full Text :
- https://doi.org/10.1016/j.bbrc.2016.03.099