Enhanced UV Resistance Role of Death Domain-Associated Protein in Human MDA-MB-231 Breast Cancer Cells by Regulation of G2 DNA Damage Checkpoint.
Enhanced UV Resistance Role of Death Domain-Associated Protein in Human MDA-MB-231 Breast Cancer Cells by Regulation of G2 DNA Damage Checkpoint.
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通过调节 G2 DNA 损伤检查点增强人 MDA-MB-231 乳腺癌细胞死亡结构域相关蛋白的紫外线抵抗作用。
DOI：
10.1177/0963689720920277
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发表时间：
2020-01
影响因子：
3.3
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Shan Z;Liu L;Shen J;Hao H;Zhang H;Lei L;Liu F;Wang Z
死亡结构域相关蛋白（DAXX）是一种多功能核蛋白，参与细胞凋亡、转录、脱氧核糖核酸损伤反应和肿瘤发生。然而，DAXX在乳腺癌发展和进展中的作用仍然难以捉摸。在这项研究中，我们研究了DAXX在人类乳腺癌样本和细胞系中的表达模式和功能。免疫组化法分析DAXX的表达和定位模式。此外，我们研究了DAXX是否在MDA-MB-231乳腺癌细胞（在MD安德森从浸润性导管癌患者的胸腔积液中分离）中对紫外线（UV）照射诱导的损伤的细胞反应中发挥内在作用。我们的研究结果表明，与对照组织相比，乳腺癌组织中的细胞核大小，染色质组织和DAXX定位发生了变化。与良性乳腺组织中的胞浆和胞核表达相比，DAXX与早幼粒细胞白血病共定位于具有颗粒分布的细胞核中。在MDA-MB-231细胞中，内源性DAXX信使核糖核酸水平在UV辐射后上调。DAXX缺陷细胞倾向于比对照细胞对辐射更敏感。相反，DAXX过表达细胞表现出磷酸化组蛋白H2 AX（γ-H2 AX）积累减少，细胞存活增加，并对UV诱导的损伤具有抗性。DAXX的保护作用可能与激活Gap 2/有丝分裂（G2/M）检查点中的共济失调毛细血管扩张突变（ATM）-检查点激酶2（ATM-CHK 2）-细胞分裂周期25 c（CDC 25 c）信号通路并最终将细胞周期阻滞在G2/M期有关。总之，这些结果表明DAXX可能是乳腺癌发生、恶性进展和放射抗性的重要组成部分。
Death domain–associated protein (DAXX) is a multifunctional nuclear protein involved in apoptosis, transcription, deoxyribonucleic acid damage response, and tumorigenesis. However, the role of DAXX in breast cancer development and progression remains elusive. In this study, we examined the expression patterns and function of DAXX in human breast cancer samples and cell lines. Immunohistochemistry was used to analyze the expression and localization patterns of DAXX. Additionally, we investigated whether DAXX played an intrinsic role in the cellular response to damage induced by ultraviolet (UV) irradiation in MDA-MB-231 breast cancer cells (isolated at M D Anderson from a pleural effusion of a patient with invasive ductal carcinoma). Our results showed that nucleus size, chromatin organization, and DAXX localization were altered in breast cancer tissues compared with those in control tissues. Compared with cytoplasmic and nuclear expression in benign breast tissues, DAXX was colocalized with promyelocytic leukemia in nuclei with a granular distribution. Endogenous DAXX messenger ribonucleic acid levels were upregulated upon UV radiation in MDA-MB-231 cells. DAXX-deficient cells tended to be more sensitive to irradiation than control cells. Conversely, DAXX-overexpressing cells exhibited reduced phosphorylated histone H2AX (γ-H2AX) accumulation, increased cell survival, and resistance to UV-induced damage. The protective effects of DAXX may be related to the activation of the ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 (ATM-CHK2)-cell division cycle 25c (CDC25c) signaling pathways in Gap2/Mitosis (G2/M) checkpoint and ultimately cell cycle arrest at G2/M phase. Taken together, these results suggested that DAXX may be an essential component in breast cancer initiation, malignant progression, and radioresistance.
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硫烷通过人类卵巢癌细胞中的细胞周期蛋白B1/CDC2的阻断在G2/M期诱导细胞周期停滞。
影响因子：
4
作者：
Chang CC;Hung CM;Yang YR;Lee MJ;Hsu YC
通讯作者：
Hsu YC
DAXX 作为肿瘤抑制剂，影响 DNA 损伤修复并使 BRCA 熟练的 TNBC 细胞对 PARP 抑制剂敏感
影响因子：
4.8
作者：
Shi, Yaqin;Jin, Juan;Guan, Xiaoxiang
通讯作者：
Guan, Xiaoxiang
DOI：
10.4161/cc.26988
发表时间：
2014
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Corpet A;Olbrich T;Gwerder M;Fink D;Stucki M
通讯作者：
Stucki M
影响因子：
3.8
作者：
Naik, Hiten;Leung, Bonnie;Ho, Cheryl
通讯作者：
Ho, Cheryl
DOI：
10.1097/pas.0b013e3182417d36
发表时间：
2012-02
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Yachida S;Vakiani E;White CM;Zhong Y;Saunders T;Morgan R;de Wilde RF;Maitra A;Hicks J;Demarzo AM;Shi C;Sharma R;Laheru D;Edil BH;Wolfgang CL;Schulick RD;Hruban RH;Tang LH;Klimstra DS;Iacobuzio-Donahue CA
通讯作者：
Iacobuzio-Donahue CA