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Protection against DNA damage-induced apoptosis by the angiogenic factor thymidine phosphorylase

Authors
 Hei-Cheul Jeung  ;  Xiao-Fang Che  ;  Misako Haraguchi  ;  Hong-Ye Zhao  ;  Tatsuhiko Furukawa  ;  Takenari Gotanda  ;  Chun-Lei Zheng  ;  Kengo Tsuneyoshi  ;  Tomoyuki Sumizawa  ;  Jae Kyung Roh  ;  Shin-ichi Akiyama 
Citation
 FEBS LETTERS, Vol.580(5) : 1294-1302, 2006 
Journal Title
 FEBS LETTERS 
ISSN
 0014-5793 
Issue Date
2006
MeSH
Angiogenesis Inducing Agents ; Antineoplastic Agents/antagonists & inhibitors ; Antineoplastic Agents/pharmacology ; Apoptosis* ; Cell Line ; DNA Damage* ; G1 Phase ; Gene Expression Regulation, Enzymologic/drug effects ; Humans ; Phosphatidylinositol 3-Kinases/metabolism ; Promoter Regions, Genetic ; Thymidine Phosphorylase/genetics ; Thymidine Phosphorylase/physiology* ; Transfection ; Tumor Suppressor Protein p53
Keywords
Thymidine phosphorylase ; Apoptosis ; Akt
Abstract
Thymidine phosphorylase (TP) is involved both in pyrimidine nucleoside metabolism and in angiogenesis. TP also conferred the resistance to hypoxia-induced apoptosis of the cancer cells. In U937 cells, DNA damage-inducing agents significantly enhanced the expression of TP. Cell lines stably transfected with TP cDNA were more resistant to the DNA damage-inducing agents than the mock-transfected cells and showed augmented activity of Akt. The cytoprotective function of TP against DNA damage was independent of its enzymatic activity. The resistance to apoptosis was partially abrogated by treatment with the phosphatidyl inositol 3-kinase (PI3K) inhibitors, suggesting that the cytoprotective function of TP is mediated, at least in part, by regulation of the PI3K/Akt pathway. These findings indicate that TP expression in increased by various stress including DNA damage and that TP molecules confer resistance to DNA damage-induced apoptosis in cancer cells.
Files in This Item:
T200603778.pdf Download
DOI
10.1016/j.febslet.2006.01.047
Appears in Collections:
5. Research Institutes (연구소) > Cancer Metastasis Research Center (암전이연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Roh, Jae Kyung(노재경)
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/110873
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