神经调节蛋白 1-表皮生长因子受体轴作为高血糖记忆效应在乳腺癌中关键介质。
Neuregulin 1-HER axis as a key mediator of hyperglycemic memory effects in breast cancer.
机构信息
Touchstone Diabetes Center and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
出版信息
Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):21058-63. doi: 10.1073/pnas.1214400109. Epub 2012 Dec 3.
Abstract
Poor outcomes in diabetic patients are observed across a range of human tumors, suggesting that cancer cells develop unique characteristics under diabetic conditions. Cancer cells exposed to hyperglycemic insults acquire permanent aggressive traits of tumor growth, even after a return to euglycemic conditions. Comparative genome-wide mapping of hyperglycemia-specific open chromatin regions and concomitant mRNA expression profiling revealed that the neuregulin-1 gene, encoding an established endogenous ligand for the HER3 receptor, is activated through a putative distal enhancer. Our findings highlight the targeted inhibition of NRG1-HER3 pathways as a potential target for the treatment breast cancer patients with associated diabetes.
摘要
在多种人类肿瘤中，糖尿病患者的预后较差，这表明癌细胞在糖尿病条件下会发展出独特的特征。即使在恢复到正常血糖水平后，暴露于高血糖刺激下的癌细胞也会获得永久性的肿瘤生长侵袭性特征。对高血糖特异性开放染色质区域和伴随的 mRNA 表达谱进行比较基因组-wide 作图显示，神经调节蛋白 1 基因（编码 HER3 受体的既定内源性配体）通过假定的远端增强子被激活。我们的研究结果强调了靶向抑制 NRG1-HER3 通路作为治疗合并糖尿病的乳腺癌患者的潜在靶点。
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