Functional impairment of telomerase in sublines derived from human lung adenocarcinoma exposed to mild oxidative stress

详细信息    查看全文

• 作者：Yoshinori Katakura ; Kaichi Yoshizaki ; Tomoharu Yasuda ; Takahiro Tsunematsu ; Norihisa Uehara ; Takumi Miura ; Tsukasa Fujiki and Sanetaka Shirahata
• 关键词：Hydrogen peroxide ; Telomerase ; Telomere ; Nuclear localization ; Tumorigenicity
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：334
• 期：2
• 页码：450-459
• 全文大小：797 K

文摘

We investigated the effects of a sublethal concentration of H₂O₂ on cancer cells by using sublines derived from human lung adenocarcinoma cell line A549 cells exposed to 200 μM H₂O₂. 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.