乳腺癌中的GATA3：肿瘤抑制因子还是癌基因？
GATA3 in Breast Cancer: Tumor Suppressor or Oncogene?
作者信息
Takaku Motoki, Grimm Sara A, Wade Paul A
机构信息
Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Science, Research Triangle Park, NC, USA.
出版信息
Gene Expr. 2015;16(4):163-8. doi: 10.3727/105221615X14399878166113.
Abstract
GATA3 is a highly conserved, essential transcription factor expressed in a number of tissues, including the mammary gland. GATA3 expression is required for normal development of the mammary gland where it is estimated to be the most abundant transcription factor in luminal epithelial cells. In breast cancer, GATA3 expression is highly correlated with the luminal transcriptional program. Recent genomic analysis of human breast cancers has revealed high-frequency mutation in GATA3 in luminal tumors, suggesting "driver" function(s). Here we discuss mutation of GATA3 in breast cancer and the potential mechanism(s) by which mutation may lead to a growth advantage in cancer.
摘要
GATA3是一种高度保守的必需转录因子，在包括乳腺在内的多种组织中表达。乳腺的正常发育需要GATA3的表达，据估计它是腔上皮细胞中最丰富的转录因子。在乳腺癌中，GATA3的表达与腔转录程序高度相关。最近对人类乳腺癌的基因组分析显示，腔肿瘤中GATA3存在高频突变，提示其具有“驱动”功能。在此，我们讨论乳腺癌中GATA3的突变以及突变可能导致癌症生长优势的潜在机制。
相似文献
1
GATA3 in Breast Cancer: Tumor Suppressor or Oncogene?乳腺癌中的GATA3：肿瘤抑制因子还是癌基因？
Gene Expr. 2015;16(4):163-8. doi: 10.3727/105221615X14399878166113.
2
Mutant GATA3 Actively Promotes the Growth of Normal and Malignant Mammary Cells.突变型GATA3可积极促进正常和恶性乳腺细胞的生长。
Anticancer Res. 2018 Aug;38(8):4435-4441. doi: 10.21873/anticanres.12745.
3
Progesterone receptor activation downregulates GATA3 by transcriptional repression and increased protein turnover promoting breast tumor growth.孕激素受体激活通过转录抑制和增加蛋白质周转来下调GATA3，从而促进乳腺肿瘤生长。
Breast Cancer Res. 2014 Dec 6;16(6):491. doi: 10.1186/s13058-014-0491-x.
4
Shift in GATA3 functions, and GATA3 mutations, control progression and clinical presentation in breast cancer.GATA3功能的转变以及GATA3突变控制着乳腺癌的进展和临床表现。
Breast Cancer Res. 2014 Nov 20;16(6):464. doi: 10.1186/s13058-014-0464-0.
5
Loss of function of GATA3 induces basal-like mammary tumors.GATA3 功能丧失导致基底样乳腺肿瘤。
Theranostics. 2022 Jan 1;12(2):720-733. doi: 10.7150/thno.65796. eCollection 2022.
6
The Significance and Therapeutic Potential of GATA3 Expression and Mutation in Breast Cancer: A Systematic Review.GATA3 表达与突变在乳腺癌中的意义及治疗潜能：系统综述
Med Res Rev. 2015 Nov;35(6):1300-15. doi: 10.1002/med.21362. Epub 2015 Aug 27.
7
Cancer-specific mutation of GATA3 disrupts the transcriptional regulatory network governed by Estrogen Receptor alpha, FOXA1 and GATA3.GATA3 的癌症特异性突变破坏了由雌激素受体 α、FOXA1 和 GATA3 调控的转录调控网络。
Nucleic Acids Res. 2020 May 21;48(9):4756-4768. doi: 10.1093/nar/gkaa179.
8
3/ drives aggressive breast cancer progression by down-regulation of GATA3 expression.3 通过下调GATA3表达驱动侵袭性乳腺癌进展。
Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3169-3174. doi: 10.1073/pnas.1701690114. Epub 2017 Mar 3.
9
GATA3 mutations define a unique subtype of luminal-like breast cancer with improved survival.GATA3 突变定义了一种独特的腔面样乳腺癌亚型，其生存得到改善。
Cancer. 2014 May 1;120(9):1329-37. doi: 10.1002/cncr.28566. Epub 2014 Jan 29.
10
Breast tumor specific mutation in GATA3 affects physiological mechanisms regulating transcription factor turnover.GATA3基因中的乳腺肿瘤特异性突变影响调节转录因子周转的生理机制。
BMC Cancer. 2014 Apr 22;14:278. doi: 10.1186/1471-2407-14-278.
引用本文的文献
1
Multi-context modeling of driver pathways reveals common and specific mechanisms across 23 cancer types.驱动通路的多背景建模揭示了23种癌症类型中的共同和特定机制。
PLoS Comput Biol. 2025 Aug 6;21(8):e1013349. doi: 10.1371/journal.pcbi.1013349. eCollection 2025 Aug.
2
Discovery of epigenetically silenced tumour suppressor genes in aggressive breast cancer through a computational approach.通过计算方法在侵袭性乳腺癌中发现表观遗传沉默的肿瘤抑制基因。
NAR Cancer. 2025 Jun 18;7(2):zcaf020. doi: 10.1093/narcan/zcaf020. eCollection 2025 Jun.
3
3Mont: A multi-omics integrative tool for breast cancer subtype stratification.3Mont：一种用于乳腺癌亚型分层的多组学整合工具。
PLoS One. 2025 Jun 27;20(6):e0326154. doi: 10.1371/journal.pone.0326154. eCollection 2025.
4
Pioneering new enhancers by GATA3: role of facilitating transcription factors and chromatin remodeling.GATA3开创新型增强子：促进转录因子和染色质重塑的作用
Nucleic Acids Res. 2025 Jun 6;53(11). doi: 10.1093/nar/gkaf473.
5
Genomic and proteomic profiling of GATA3 mutant metastatic hormone receptor-positive breast cancer and impact on clinical outcomes.GATA3突变转移性激素受体阳性乳腺癌的基因组和蛋白质组分析及其对临床结局的影响。
Breast Cancer Res Treat. 2025 May 29. doi: 10.1007/s10549-025-07710-w.
6
T-helper Transcription Factor Profiling in Peripheral Blood Mononuclear Cells: A Non-invasive Approach to Predicting Disease Stage in Breast Cancer.外周血单个核细胞中辅助性T细胞转录因子分析：一种预测乳腺癌疾病分期的非侵入性方法。
Biochem Genet. 2025 May 16. doi: 10.1007/s10528-025-11133-z.
7
Enhancing cancer subtype classification through convolutional neural networks: a deepinsight analysis of TCGA gene expression data.通过卷积神经网络增强癌症亚型分类：对TCGA基因表达数据的深入分析
Health Inf Sci Syst. 2025 Apr 28;13(1):33. doi: 10.1007/s13755-025-00349-3. eCollection 2025 Dec.
8
Learning tissue representation by identification of persistent local patterns in spatial omics data.通过识别空间组学数据中的持续局部模式来学习组织表征。
Nat Commun. 2025 Apr 30;16(1):4071. doi: 10.1038/s41467-025-59448-0.
9
Super-enhancer profiling reveals ThPOK/ZBTB7B, a CD4+ cell lineage commitment factor, as a master regulator that restricts breast cancer cells to a luminal non-migratory phenotype.超级增强子分析揭示了ThPOK/ZBTB7B（一种CD4 +细胞谱系决定因子）是一种主要调节因子，它将乳腺癌细胞限制为管腔非迁移表型。
Res Sq. 2025 Mar 31:rs.3.rs-6240646. doi: 10.21203/rs.3.rs-6240646/v1.
10
Racial Differences in ctDNA Profiles, Targeted Therapy Use, and Outcomes in Metastatic Breast Cancer.转移性乳腺癌中循环肿瘤DNA（ctDNA）特征、靶向治疗应用及预后的种族差异
JAMA Netw Open. 2025 Feb 3;8(2):e2461899. doi: 10.1001/jamanetworkopen.2024.61899.
本文引用的文献
1
GATA-3 function in innate and adaptive immunity.GATA-3 在先天免疫和适应性免疫中的作用。
Immunity. 2014 Aug 21;41(2):191-206. doi: 10.1016/j.immuni.2014.06.006.
2
Breast tumor specific mutation in GATA3 affects physiological mechanisms regulating transcription factor turnover.GATA3基因中的乳腺肿瘤特异性突变影响调节转录因子周转的生理机制。
BMC Cancer. 2014 Apr 22;14:278. doi: 10.1186/1471-2407-14-278.
3
The role of prolyl hydroxylase domain protein (PHD) during rosiglitazone-induced adipocyte differentiation.脯氨酰羟化酶结构域蛋白（PHD）在罗格列酮诱导的脂肪细胞分化过程中的作用。
J Biol Chem. 2014 Jan 31;289(5):2755-64. doi: 10.1074/jbc.M113.493650. Epub 2013 Dec 12.
4
Cancer genome landscapes.肿瘤基因组图谱。
Science. 2013 Mar 29;339(6127):1546-58. doi: 10.1126/science.1235122.
5
Gata3 antagonizes cancer progression in Pten-deficient prostates.Gata3 拮抗 Pten 缺陷前列腺癌的进展。
Hum Mol Genet. 2013 Jun 15;22(12):2400-10. doi: 10.1093/hmg/ddt088. Epub 2013 Feb 20.
6
Identification of the E3 deubiquitinase ubiquitin-specific peptidase 21 (USP21) as a positive regulator of the transcription factor GATA3.鉴定 E3 去泛素化酶泛素特异性肽酶 21（USP21）作为转录因子 GATA3 的正调控因子。
J Biol Chem. 2013 Mar 29;288(13):9373-82. doi: 10.1074/jbc.M112.374744. Epub 2013 Feb 10.
7
GATA3 suppresses metastasis and modulates the tumour microenvironment by regulating microRNA-29b expression.GATA3 通过调控 microRNA-29b 的表达抑制转移并调节肿瘤微环境。
Nat Cell Biol. 2013 Feb;15(2):201-13. doi: 10.1038/ncb2672. Epub 2013 Jan 27.
8
GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility.GATA3 通过塑造增强子可及性在上游调控 FOXA1 介导的 ESR1 结合。
Genome Res. 2013 Jan;23(1):12-22. doi: 10.1101/gr.139469.112. Epub 2012 Nov 21.
9
Comprehensive molecular portraits of human breast tumours.人类乳腺肿瘤的全面分子特征图谱。
Nature. 2012 Oct 4;490(7418):61-70. doi: 10.1038/nature11412. Epub 2012 Sep 23.
10
Impaired proteasome function activates GATA3 in T cells and upregulates CTLA-4: relevance for Sézary syndrome.蛋白酶体功能受损可激活 T 细胞中的 GATA3，并上调 CTLA-4：与 Sézary 综合征相关。
J Invest Dermatol. 2013 Jan;133(1):249-57. doi: 10.1038/jid.2012.265. Epub 2012 Sep 6.
Zotero 插件