Functional impairment of telomerase in sublines derived from human lung adenocarcinoma exposed to mild oxidative stress.
We investigated the effects of a sublethal concentration of H(2)O(2) on cancer cells by using sublines derived from human lung adenocarcinoma cell line A549 cells exposed to 200 microM H(2)O(2). These sublines (AST cells) showed an elongated morphology distinct from the rounded morphology of A549 cells. Notably, AST cells demonstrated telomere shortening despite displaying telomerase activity and expressing human telomerase reverse transcriptase (hTERT). This functional impairment of telomerase occurred due to perturbed subcellular localization of hTERT in AST cells. Endogenous as well as ectopically expressed hTERT was localized in the nuclei of A549 cells; however, in AST cells, the localization was mainly in the cytoplasm. Furthermore, these AST cells demonstrated decreased tumorigenic features both in vitro and in vivo. These results suggest that depletion of hTERT from nuclei not only endows cancer cells with a finite replicative life span accompanied by telomere shortening, but also decreases the tumorigenicity of cancer cells.
Katakura
Yoshinori
Y
Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan. katakura@grt.kyushu-u.ac.jp
Yoshizaki
Kaichi
K
Yasuda
Tomoharu
T
Tsunematsu
Takahiro
T
Uehara
Norihisa
N
Miura
Takumi
T
Fujiki
Tsukasa
T
Shirahata
Sanetaka
S
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology*; D018384:Oxidative Stress; D010641:Phenotype; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000187:drug effects / Q000648:ultrastructure
D006861:Hydrogen Peroxide; D019098:Telomerase