Chen Yinghua, Olopade Olufunmilayo I
Department of Medicine, Center for Clinical Cancer Genetics, University of Chicago, Chicago, IL 60637, USA.
Expert Rev Anticancer Ther. 2008 Oct;8(10):1689-98. doi: 10.1586/14737140.8.10.1689.
Breast cancer is the second leading cause of cancer deaths and is the most frequently diagnosed cancer in women of industrialized nations. Breast cancer progression is a multistep process involving genetic and epigenetic alterations that drive normal breast cells into highly malignant derivatives with metastatic potential. MYC is a proto-oncogene whose protein product contains a basic helix-loop-helix domain. MYC functions as a transcription factor regulating up to 15% of all human genes. MYC is regulated at multiple levels, and the protein is a downstream effector of several signaling pathways. In breast cancer cells, MYC target genes are involved in cell growth, transformation, angiogenesis and cell-cycle control. BRCA1 is linked to transcriptional regulation through interaction with MYC. Although the relationship between amplification and overexpression is not clearly delineated, MYC amplification is significantly correlated with aggressive tumor phenotypes and poor clinical outcomes. MYC amplification is emerging as an important predictor of response to HER2-targeted therapies and its role in BRCA1-associated breast cancer makes it an important target in basal-like/triple-negative breast cancers.
乳腺癌是癌症死亡的第二大主要原因,也是工业化国家女性中最常被诊断出的癌症。乳腺癌的进展是一个多步骤过程,涉及基因和表观遗传改变,这些改变会将正常乳腺细胞转变为具有转移潜能的高度恶性衍生物。MYC是一种原癌基因,其蛋白质产物包含一个碱性螺旋-环-螺旋结构域。MYC作为一种转录因子,可调节多达15%的人类基因。MYC在多个水平受到调控,该蛋白质是多种信号通路的下游效应器。在乳腺癌细胞中,MYC靶基因参与细胞生长、转化、血管生成和细胞周期控制。BRCA1通过与MYC相互作用与转录调控相关联。尽管扩增与过表达之间的关系尚未明确界定,但MYC扩增与侵袭性肿瘤表型和不良临床结果显著相关。MYC扩增正成为对HER2靶向治疗反应的重要预测指标,其在BRCA1相关乳腺癌中的作用使其成为基底样/三阴性乳腺癌的重要靶点。