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Protection against DNA damage‐induced apoptosis by the angiogenic factor thymidine phosphorylase
Author(s) -
Jeung Hei-Cheul,
Che Xiao-Fang,
Haraguchi Misako,
Zhao Hong-Ye,
Furukawa Tatsuhiko,
Gotanda Takenari,
Zheng Chun-Lei,
Tsuneyoshi Kengo,
Sumizawa Tomoyuki,
Roh Jae Kyung,
Akiyama Shin-ichi
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.01.047
Subject(s) - dna damage , transfection , apoptosis , thymidine phosphorylase , microbiology and biotechnology , biology , protein kinase b , chemistry , cancer cell , dna , cancer research , cell culture , biochemistry , enzyme , cancer , genetics
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.