K-RAS transformation in prostate epithelial cell overcomes H 2O 2-induced apoptosis via upregulation of gamma-glutamyltransferase-2

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Title
K-RAS transformation in prostate epithelial cell overcomes H 2O 2-induced apoptosis via upregulation of gamma-glutamyltransferase-2
Author(s)
D O Moon; Bo Yeon KimJae-Hyuk JangMun-Ock Kim; R G P T Jayasooriya; C H Kang; Y H Choi; S K Moon; W J Kim; Jong Seog Ahn; G Y Kim
Bibliographic Citation
Toxicology in Vitro, vol. 26, no. 3, pp. 429-434
Publication Year
2012
Abstract
The anti-apoptotic oncogene K-RAS is hypothesized to increase the antioxidant status of cells, thereby protecting them from generation of reactive oxygen species (ROS). Therefore, we examined whether K-RAS overcomes hydrogen peroxide (H 2O 2)-mediated apoptosis in the human fetal prostate epithelial cell 267B1. In this study, we found that treatment of 267B1 cells with H 2O 2 resulted in significant reduction of cell growth, which was associated with cytochrome-c release and caspase-3 activation. However, mutated K-RAS transformation (268B1/K-RAS) rendered 267B1 cells reduction of the resistance to H 2O 2-induced apoptosis through suppression of ROS generation. In addition, we analyzed profiling of gene expression in K-RAS transformation and found that gamma-glutamyltransferase 2 (GGT2) most highly expressed. Transient knockdown of K-RAS resulted in a significant downregulation of GGT gene expression. We also revealed that expression of GGT2 gene is closely regulated by the ERK signal pathway in 267B1/K-RAS cells. In addition, the anti-apoptotic effect of mutated K-RAS was attenuated by treatment with GGT2 RNA interference through inhibition of ROS generation, suggesting that mutated K-RAS mediates resistance to H 2O 2-induced apoptosis through GGT2 activation. These results importantly provide mechanistic insights on the anti-apoptotic activity of mutated K-RAS.
Keyword
Gamma-glutamyltransferase-2K-RASOxidative stress
ISSN
0887-2333
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.tiv.2012.01.013
Type
Article
Appears in Collections:
Ochang Branch Institute > Anticancer Agent Research Center > 1. Journal Articles
Ochang Branch Institute > Natural Medicine Research Center > 1. Journal Articles
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