切换至 "中华医学电子期刊资源库"

中华乳腺病杂志(电子版) ›› 2016, Vol. 10 ›› Issue (06) : 366 -369. doi: 10.3877/cma.j.issn.1674-0807.2016.06.009

综述

分化抑制因子2 的生物学功能及其在乳腺癌中的研究进展
温晓芬1,2, 许宏武1,3, Min Chen1, 张国君1,2,()   
  1. 1.515041 汕头大学医学院长江学者实验室
    2.515041 汕头大学医学院附属肿瘤医院乳腺内科
    3.515041 汕头大学医学院第一附属医院神经外科
  • 收稿日期:2015-12-08 出版日期:2016-12-01
  • 通信作者: 张国君
  • 基金资助:
    国家重点基础研究发展计划(2011CB70770 973)

HER-2 gene mutation in breast cancer research

Xiaofen Wen, Hongwu Xu, Guojun Zhan   

  • Received:2015-12-08 Published:2016-12-01
引用本文:

温晓芬, 许宏武, Min Chen, 张国君. 分化抑制因子2 的生物学功能及其在乳腺癌中的研究进展[J/OL]. 中华乳腺病杂志(电子版), 2016, 10(06): 366-369.

Xiaofen Wen, Hongwu Xu, Guojun Zhan. HER-2 gene mutation in breast cancer research[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2016, 10(06): 366-369.

分化抑制因子2 (ID2)属螺旋-环-螺旋蛋白(HLH)的ID 蛋白家族的一员, 调控乳腺癌的上皮间质转化(EMT),并影响乳腺癌患者的预后。 而ID2 与HLH 家族成员之间的协同作用形成了复杂的生物学调控网络,使其在乳腺癌中的生物学特性也复杂多变。 笔者对ID2 调控乳腺癌EMT 的相关研究进行了综述。

图1 小鼠乳腺组织ID2 抑制EMT 机制示意图 注:TGF-β 表示转化生长因子-β;Smad3/4 表示Smad 家族蛋白3、4;JunB 表示活化蛋白激酶1;ATF3 表示活化复制因子3;ID2 表示分化抑制因子2;E2A 表示转录因子3;E-cad 表示E-钙黏蛋白;Snail-1 表示锌指转录因子;β4-integin 表示整合素β4;EMT 表示上皮间质转化
表1 ID2 在不同肿瘤中的作用
[1]
Benezra R, Davis RL, Lockshon D,et. al. The protein id:a negative regulator of helix-loop-helix DNA binding proteins[J]. Cell, 1990,61(1):49-59.
[2]
Lasorella A, Benezra R, Iavarone A. The ID proteins: master regulators of cancer stem cells and tumour aggressiveness[J]. Nat Rev Cancer,2014,14(2):77-91.
[3]
Teng Y, Li X. The roles of HLH transcription factors in epithelial mesenchymal transition and multiple molecular mechanisms[J]. Clin Exp Metastasis,2014,31(3):367-377.
[4]
Sikder HA, Devlin MK, Dunlap S,et al. Id proteins in cell growth and tumorigenesis[J]. Cancer Cell,2003,3(6):525-530.
[5]
Janatpour MJ,McMaster MT,Genbacev O,et al. Id-2 regulates critical aspects of human cytotrophoblast differentiation, invasion and migration[J]. Development,2000,127(3):549-558.
[6]
Chen XS, Zhang YH, Cai QY,et al. ID2: a negative transcription factor regulating oligodendroglia differentiation[J]. J Neurosci Res,2012,90(5):925-932.
[7]
Park HJ, Hong M, Bronson RT,et al. Elevated Id2 expression results in precocious neural stem cell depletion and abnormal brain development[J]. Stem Cells,2013,31(5):1010-1021.
[8]
Butler DC, Haramizu S, Williamson DL,et al. Phospho-ablated Id2 is growth suppressive and pro-apoptotic in proliferating myoblasts[J].PLoS One,2009,4(7):e6302.
[9]
Sakata-Goto T, Takahashi K, Kiso H, et al. Id2 controls chondrogenesis acting downstream of BMP signaling during maxillary morphogenesis[J]. Bone,2012,50(1):69-78.
[10]
Kee BL. E and ID proteins branch out[J]. Nat Rev Immunol,2009,9(3):175-184.
[11]
Miyazaki M, Miyazaki K, Chen S, et al. The E-Id protein axis modulates the activities of the PI3K-AKT-mTORC1-Hif1a and c-myc/p19Arf pathways to suppress innate variant TFH cell development,thymocyte expansion, and lymphomagenesis[J]. Genes Dev,2015,29(4):409-425.
[12]
Kim NS, Kim HT, Kwon MC,et al. Survival and differentiation of mammary epithelial cells in mammary gland development require nuclear retention of Id2 due to RANK signaling[J]. Mol Cell Biol,2011,31(23):4775-4788.
[13]
Nakahiro T, Kurooka H, Mori K, et al. Identification of BMPresponsive elements in the mouse Id2 gene[J]. Biochem Biophys Res Commun,2010,399(3):416-421.
[14]
Belletti B, Prisco M, Morrione A, et al. Regulation of Id2 gene expression by the IGF-I receptor requires signaling by phosphatidylinositol 3-kinase[J]. J Biol Chem, 2001,276 (17):13 867-13 874.
[15]
Higgins S, Wong SH, Richner M,et al. Fibroblast growth factor 2 reactivates G1 checkpoint in SK-N-MC cells via regulation of p21,inhibitor of differentiation genes (Id1-3), and epithelium-mesenchyme transition-like events[J]. Endocrinology,2009,150(9):4044-4055.
[16]
Weigent DA. Regulation of Id2 expression in EL4 T lymphoma cells overexpressing growth hormone[J]. Cell Immunol, 2009, 255(1-2):46-54.
[17]
Guo L, Lan J, Lin Y, et al. Hypoxia/ischemia up-regulates Id2 expression in neuronal cells in vivo and in vitro[J]. Neurosci Lett,2013,554:88-93.
[18]
Wang KR, Nemoto T, Yokota Y. RFX1 mediates the serum-induced immediate early response of Id2 gene expression[J]. J Biol Chem,2007,282(36):26 167-26 177.
[19]
Kurooka H, Nakahiro T, Mori K,et al. BMP signaling is responsible for serum-induced Id2 expression[J]. Biochem Biophys Res Commun,2012,420(2):281-287.
[20]
Annibali D, Gioia U, Savino M,et al. A new module in neural differentiation control: two microRNAs upregulated by retinoic acid,miR-9 and -103, target the differentiation inhibitor ID2[J]. PLoS One,2012,7(7):e40269.
[21]
Kurooka H, Yokota Y. Nucleo-cytoplasmic shuttling of Id2, a negative regulator of basic helix-loop-helix transcription factors[J]. J Biol Chem,2005,280(6):4313-4320.
[22]
Fajerman I, Schwartz AL, Ciechanover A. Degradation of the Id2 developmental regulator: targeting via N-terminal ubiquitination[J].Biochem Biophys Res Commun,2004,314(2):505-512.
[23]
Lasorella A, Stegmuller J, Guardavaccaro D,et al. Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth[J]. Nature,2006,442(7101):471-474.
[24]
Williams SA,Maecker HL,French DM,et al. USP1 deubiquitinates ID proteins to preserve a mesenchymal stem cell program in osteosarcoma[J]. Cell,2011,146(6):918-930.
[25]
Florio M, Hernandez MC,Yang HM,et al. Id2 promotes apoptosis by a novel mechanism independent of dimerization to basic helix-loop-helix factors[J]. Mol Cell Biol,1998,18(9):5435-5444.
[26]
Guo L, Yang X, Lin X,et al. Silencing of Id2 attenuates hypoxia/ischemia-induced neuronal injury via inhibition of neuronal apoptosis[J]. Behav Brain Res,2015,292:528-536.
[27]
Alway SE, Degens H, Krishnamurthy G,et al. Potential role for Id myogenic repressors in apoptosis[J]. Am J Physiol Cell Physiol,2002,283(1):C66-76.
[28]
Cao Y, Liu X, Zhang W,et al. TGF-beta repression of Id2 induces apoptosis in gut epithelial cells[J]. Oncogene, 2009, 28(8):1089-1098.
[29]
Hua H, Sarvetnick N. ID2 promotes the expansion and survival of growth-arrested pancreatic beta cells[J]. Endocrine, 2007, 32(3):329-337.
[30]
Saika S, Ikeda K,Yamanaka O,et al. Adenoviral gene transfer of BMP-7, Id2, or Id3 suppresses injury-induced epithelial-tomesenchymal transition of lens epithelium in mice[J]. Am J Physiol Cell Physiol,2006,290(1):C282-289.
[31]
Veerasamy M, Phanish M, Dockrell ME. Smad mediated regulation of inhibitor of DNA binding 2 and its role in phenotypic maintenance of human renal proximal tubule epithelial cells[J]. PLoS One, 2013,8(1):e51842.
[32]
Kondo M, Cubillo E, Tobiume K,et al. A role for Id in the regulation of TGF-beta-induced epithelial-mesenchymal transdifferentiation[J].Cell Death Differ,2004,11(10):1092-1101.
[33]
Gervasi M, Bianchi-Smiraglia A, Cummings M,et al. JunB contributes to Id2 repression and the epithelial-mesenchymal transition in response to transforming growth factor-β[J]. J Cell Biol,2012,196(5):589-603.
[34]
Chang C, Yang X, Pursell B,et al. Id2 complexes with the SNAG domain of Snai1 inhibiting Snai1-mediated repression of integrin β4[J]. Mol Cell Biol,2013,33(19):3795-3804.
[35]
Ling F, Kang B, Sun XH. Id proteins: small molecules, mighty regulators[J]. Curr Top Dev Biol,2014,110:189-216.
[36]
Nair R,Teo WS,Mittal V,et al. ID proteins regulate diverse aspects of cancer progression and provide novel therapeutic opportunities[J]. Mol Ther,2014,22(8):1407-1415.
[37]
Wang C, Chen Q, Hamajima Y,et al. Id2 regulates the proliferation of squamous cell carcinoma in vitro via the NF-κB/Cyclin D1 pathway[J]. Chin J Cancer,2012,31(9):430-439.
[38]
Trabosh VA, Divito KA, D Aguda B,et al. Sequestration of E12/E47 and suppression of p27KIP1 play a role in Id2-induced proliferation and tumorigenesis[J]. Carcinogenesis,2009,30(7):1252-1259.
[39]
Gray MJ, Dallas NA, Van Buren G,et al. Therapeutic targeting of Id2 reduces growth of human colorectal carcinoma in the murine liver[J].Oncogene,2008,27(57):7192-7200.
[40]
Luo KL, Luo JH, Yu YP. (-)-Epigallocatechin-3-gallate induces Du145 prostate cancer cell death via downregulation of inhibitor of DNA binding 2, a dominant negative helix-loop-helix protein[J]. Cancer Sci,2010,101(3):707-712.
[41]
Ahlqvist K, Saamarthy K, Syed Khaja AS,et al. Expression of Id proteins is regulated by the Bcl-3 proto-oncogene in prostate cancer[J]. Oncogene,2013,32(12):1601-1608.
[42]
Tsunedomi R, Iizuka N, Harada S,et al. Susceptibility of hepatomaderived cells to histone deacetylase inhibitors is associated with ID2 expression[J]. Int J Oncol,2013,42(4):1159-1166.
[43]
Lasorella A, Rothschild G, Yokota Y,et al. Id2 mediates tumor initiation, proliferation, and angiogenesis in Rb mutant mice[J]. Mol Cell Biol,2005,25(9):3563-3574.
[44]
Coma S, Amin DN, Shimizu A, et al. Id2 promotes tumor cell migration and invasion through transcriptional repression of semaphorin 3F[J]. Cancer Res,2010,70(9):3823-3832.
[45]
Stighall M, Manetopoulos C, Axelson H,et al. High ID2 protein expression correlates with a favourable prognosis in patients with primary breast cancer and reduces cellular invasiveness of breast cancer cells[J]. Int J Cancer,2005,115(3):403-411.
[46]
Li K, Yao L, Chen L,et al. ID2 predicts poor prognosis in breast cancer, especially in triple-negative breast cancer, and inhibits E-cadherin expression[J]. Onco Targets Ther,2014,7:1083-1094.
[47]
Itahana Y,Singh J,Sumida T,et al. Role of Id-2 in the maintenance of a differentiated and noninvasive phenotype in breast cancer cells[J].Cancer Res,2003,63(21):7098-7105.
[48]
Appaiah H, Bhat-Nakshatri P, Mehta R,et al. ITF2 is a target of CXCR4 in MDA-MB-231 breast cancer cells and is associated with reduced survival in estrogen receptor-negative breast cancer [J].Cancer Bio Ther,2014,10(6):600-614.
[49]
Meng Y,Gu C,Wu Z,et al. Id2 promotes the invasive growth of MCF-7 and SKOV-3 cells by a novel mechanism independent of dimerization to basic helix-loop-helix factors[J]. BMC Cancer,2009,9:75.
[50]
Wong MV, Jiang S, Palasingam P,et al. A divalent ion is crucial in the structure and dominant-negative function of ID proteins, a class of helix-loop-helix transcription regulators[J]. PLoS One,2012,7(10):e48591.
[1] 李洋, 蔡金玉, 党晓智, 常婉英, 巨艳, 高毅, 宋宏萍. 基于深度学习的乳腺超声应变弹性图像生成模型的应用研究[J/OL]. 中华医学超声杂志(电子版), 2024, 21(06): 563-570.
[2] 周荷妹, 金杰, 叶建东, 夏之一, 王进进, 丁宁. 罕见成人肋骨郎格汉斯细胞组织细胞增生症被误诊为乳腺癌术后骨转移一例[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 380-383.
[3] 河北省抗癌协会乳腺癌专业委员会护理协作组. 乳腺癌中心静脉通路护理管理专家共识[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 321-329.
[4] 刘晨鹭, 刘洁, 张帆, 严彩英, 陈倩, 陈双庆. 增强MRI 影像组学特征生境分析在预测乳腺癌HER-2 表达状态中的应用[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 339-345.
[5] 张晓宇, 殷雨来, 张银旭. 阿帕替尼联合新辅助化疗对三阴性乳腺癌的疗效及预后分析[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 346-352.
[6] 邱琳, 刘锦辉, 组木热提·吐尔洪, 马悦心, 冷晓玲. 超声影像组学对致密型乳腺背景中非肿块型乳腺癌的诊断价值[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 353-360.
[7] 程燕妮, 樊菁, 肖瑶, 舒瑞, 明昊, 党晓智, 宋宏萍. 乳腺组织定位标记夹的应用与进展[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 361-365.
[8] 涂盛楠, 胡芬, 张娟, 蔡海峰, 杨俊泉. 天然植物提取物在乳腺癌治疗中的应用[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 366-370.
[9] 朱文婷, 顾鹏, 孙星. 非酒精性脂肪性肝病对乳腺癌发生发展及治疗的影响[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 371-375.
[10] 葛睿, 陈飞, 李杰, 李娟娟, 陈涵. 多基因检测在早期乳腺癌辅助治疗中的应用价值[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(05): 257-263.
[11] 韩萌萌, 冯雪园, 马宁. 乳腺癌改良根治术后桡神经损伤1例[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 117-118.
[12] 高杰红, 黎平平, 齐婧, 代引海. ETFA和CD34在乳腺癌中的表达及与临床病理参数和预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 64-67.
[13] 张志兆, 王睿, 郜苹苹, 王成方, 王成, 齐晓伟. DNMT3B与乳腺癌预后的关系及其生物学机制[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 624-629.
[14] 王玲艳, 高春晖, 冯雪园, 崔鑫淼, 刘欢, 赵文明, 张金库. 循环肿瘤细胞在乳腺癌新辅助及术后辅助治疗中的应用[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 630-633.
[15] 赵林娟, 吕婕, 王文胜, 马德茂, 侯涛. 超声引导下染色剂标记切缘的梭柱型和圆柱型保乳区段切除术的效果研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 634-637.
阅读次数
全文


摘要