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Research Paper
TRF2 Promotes Multidrug Resistance in Gastric Cancer Cells
Hanbing Ning, Tingting Li, Lina Zhao, Ting Li, Jichang Li, Jie Liu, Zhiguo Liu and Daiming Fan
volume 5 | issue 8
august 2006Pages: 950 - 956
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The role of telomere in drug resistance has not been clearly understood. Recent studies have been focused on telomerase activity and telomere length, but the findings are still controversial. It’s been found that DNA double-strand breaks induced by anticancer drugs or irradiation increase TRF2 expression as an early response to DNA damage, which inhibits activation of ATM-dependent DNA damage response network, indicating TRF2 might probably be a general DNA-repair factor rather than merely a telomere-binding factor. In this study, the possible involvement of telomerase, telomere and TRF2 in DNA damage response and drug resistance was investigated. Telomere length was found elongated in multidrug-resistant variants of gastric cancer cell line SGC7901 treated with adriamycin or etoposide, however, drug-treatment per se had no effect on telomere length. Telomerase activity and TRF2 expression were up-regulated after treatment, but not TRF1. TRF2 up-regulation was more dramatic in drug-resistant cells and occurred before the expression of ATM, ?H2AX, and p53. Moreover, TRF2 inhibited the expression of ATM-dependent DSB responsive genes. Inhibition of TRF2 expression by RNA interference in drug-resistant cells partially reversed its resistance phenotype and over-expression of TRF2 in SGC7901 promoted its resistance phenotype. Taken together, current results indicate that TRF2 plays an important role in DNA damage response, and is involved in drug resistance of gastric cancer. Further study of the biological functions of TRF2 might be helpful to dissect the molecular mechanism of multiple drug-resistance and generate novel target to overcome it.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.