TY - JOUR
T1 - Functional impairment of telomerase in sublines derived from human lung adenocarcinoma exposed to mild oxidative stress
AU - Katakura, Yoshinori
AU - Yoshizaki, Kaichi
AU - Yasuda, Tomoharu
AU - Tsunematsu, Takahiro
AU - Uehara, Norihisa
AU - Miura, Takumi
AU - Fujiki, Tsukasa
AU - Shirahata, Sanetaka
N1 - Funding Information:
We thank M. Yoshida (The University of Tokyo), G. Grosveld (St. Jude Children’s Research Hospital), and R. Weinberg (Whitehead Institute) for generously donating leptomycin B, the expression plasmid for human CRM1, and the expression plasmid for hTERT, respectively. This work was supported in part by the Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science.
PY - 2005/8/26
Y1 - 2005/8/26
N2 - We investigated the effects of a sublethal concentration of H 2O2 on cancer cells by using sublines derived from human lung adenocarcinoma cell line A549 cells exposed to 200 μM H 2O2. 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.
AB - We investigated the effects of a sublethal concentration of H 2O2 on cancer cells by using sublines derived from human lung adenocarcinoma cell line A549 cells exposed to 200 μM H 2O2. 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.
KW - Hydrogen peroxide
KW - Nuclear localization
KW - Telomerase
KW - Telomere
KW - Tumorigenicity
UR - http://www.scopus.com/inward/record.url?scp=22144463518&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22144463518&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2005.06.109
DO - 10.1016/j.bbrc.2005.06.109
M3 - Article
C2 - 16004965
AN - SCOPUS:22144463518
SN - 0006-291X
VL - 334
SP - 450
EP - 459
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -
