乳腺癌
铁蛋白
癌症
癌症研究
转铁蛋白受体
基因敲除
铁转运蛋白
医学
内科学
内分泌学
生物
转铁蛋白
肿瘤科
海西定
贫血
基因
遗传学
作者
Wei Wang,Zhiyong Deng,Heather Hatcher,Lance D. Miller,Xiumin Di,Lia Tesfay,Guangchao Sui,Ralph B. D’Agostino,Frank M. Torti,Suzy V. Torti
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2014-01-15
卷期号:74 (2): 497-507
被引量:101
标识
DOI:10.1158/0008-5472.can-13-1224
摘要
Abstract Experimental and epidemiologic evidence suggests that dysregulation of proteins involved in iron metabolism plays a critical role in cancer. The mechanisms by which cancer cells alter homeostatic iron regulation are just beginning to be understood. Here, we demonstrate that iron regulatory protein 2 (IRP2) plays a key role in iron accumulation in breast cancer. Although both IRP1 and IRP2 are overexpressed in breast cancer, the overexpression of IRP2, but not IRP1, is associated with decreased ferritin H and increased transferrin receptor 1 (TfR1). Knockdown of IRP2 in triple-negative MDA-MB-231 human breast cancer cells increases ferritin H expression and decreases TfR1 expression, resulting in a decrease in the labile iron pool. Further, IRP2 knockdown reduces growth of MDA-MB-231 cells in the mouse mammary fat pad. Gene expression microarray profiles of patients with breast cancer demonstrate that increased IRP2 expression is associated with high-grade cancer. Increased IRP2 expression is observed in luminal A, luminal B, and basal breast cancer subtypes, but not in breast tumors of the ERBB2 molecular subtype. These results suggest that dysregulation of IRP2 is an early nodal point underlying altered iron metabolism in breast cancer and may contribute to poor outcome of some patients with breast cancer. Cancer Res; 74(2); 497–507. ©2013 AACR.
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