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ID4调控正常乳腺上皮中的管腔谱系定向分化,并在基底样乳腺癌中抑制BRCA1功能。

ID4 controls luminal lineage commitment in normal mammary epithelium and inhibits BRCA1 function in basal-like breast cancer.

作者信息

Baker Laura A, Holliday Holly, Swarbrick Alexander

机构信息

The Kinghorn Cancer Centre and Cancer Research DivisionGarvan Institute of Medical Research, Darlinghurst, New South Wales, Australia St Vincent's Clinical SchoolFaculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.

The Kinghorn Cancer Centre and Cancer Research DivisionGarvan Institute of Medical Research, Darlinghurst, New South Wales, Australia St Vincent's Clinical SchoolFaculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia

出版信息

Endocr Relat Cancer. 2016 Sep;23(9):R381-92. doi: 10.1530/ERC-16-0196. Epub 2016 Jul 13.

Abstract

Inhibitor of differentiation (ID) proteins are key regulators of development and tumorigenesis. One member of this family, ID4, controls lineage commitment during mammary gland development by acting upstream of key developmental pathways. Recent evidence suggests an emerging role for ID4 as a lineage-dependent proto-oncogene that is overexpressed and amplified in a subset of basal-like breast cancers (BLBCs), conferring poor prognosis. Several lines of evidence suggest ID4 may suppress BRCA1 function in BLBC and in doing so, define a subset of BLBC patients who may respond to therapies traditionally used in BRCA1-mutant cancers. This review highlights recent advances in our understanding of the requirement for ID4 in mammary lineage commitment and the role for ID4 in BLBC. We address current shortfalls in this field and identify important areas of future research.

摘要

分化抑制因子(ID)蛋白是发育和肿瘤发生的关键调节因子。该家族的一个成员ID4,通过在关键发育途径的上游发挥作用,控制乳腺发育过程中的谱系定向。最近的证据表明,ID4作为一种谱系依赖性原癌基因,在一部分基底样乳腺癌(BLBC)中过度表达并扩增,预示着不良预后,其作用日益凸显。多条证据表明,ID4可能在BLBC中抑制BRCA1功能,如此一来,可确定一部分可能对传统用于BRCA1突变癌症的疗法有反应的BLBC患者。本综述重点介绍了我们对ID4在乳腺谱系定向中的需求以及ID4在BLBC中的作用的最新认识进展。我们讨论了该领域当前的不足,并确定了未来研究的重要领域。

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