Deleted in breast cancer 1 (DBC1) deficiency results in apoptosis of breast cancer cells through impaired responses to UV-induced DNA damage

被引：25

作者：

Kim, Wootae

Kim, Ja-Eun ^{[1
]}

机构：

[1] Kyung Hee Univ, Sch Med, Dept Pharmacol, Seoul 130701, South Korea

来源：

CANCER LETTERS | 2013年 / 333卷 / 02期

基金：

新加坡国家研究基金会;

关键词：

DBC1; DNA damage; UV irradiation; Checkpoint; Apoptosis; NUCLEOTIDE EXCISION-REPAIR; SIRT1; DEACETYLASE; GENOMIC STABILITY; PROTEIN; EXPRESSION; PHOSPHORYLATION; IDENTIFICATION; ACETYLATION; REGULATOR; ATM;

D O I：

10.1016/j.canlet.2013.01.026

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

DBC1 (deleted in breast cancer 1) participates in the regulation of cell survival and death in response to various stimuli. In particular, DBC1 promotes cell death upon DNA damage through inhibition of SIRT1 deacetylase. However, the SIRT1-independent functions of DBC1 in the regulation of DNA damage response are less well understood. Therefore, we analyzed the DNA damage response in Hs578T breast cancer cell line in which the DBC1-SIRT1 interaction is barely detectable. DBC1-siRNA transfected cells showed a failure in the DNA damage checkpoint and the accumulation of genomic damage following UV irradiation. In addition, DBC1-deficient cells exhibited less JNK activation. Finally, the interruptions of signaling in DBC1-depleted cells contributed to cell death in response to UV irradiation. Overall, these data suggest that DBC1 is essential for a fully efficient and effective response to UV irradiation. Therefore, DBC1 plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

引用

页码：180 / 186

页数：7

共 44 条

[1]

Bode Ann M, 2003, Sci STKE, V2003, pRE2, DOI 10.1126/stke.2003.167.re2

[2] SIRT1 confers protection against UVB- and H2O2-induced cell death via modulation of p53 and JNK in cultured skin keratinocytes [J].