IRP2 Regulates Breast Tumor Growth
| Autor: | Suzy V. Torti, Lia Tesfay, Ralph B. D'Agostino, Wei Wang, Heather Hatcher, Guangchao Sui, Frank M. Torti, Zhiyong Deng, Lance D. Miller, Xiumin Di |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
medicine.medical_specialty Iron Mice Nude Apoptosis Breast Neoplasms Transferrin receptor Biology Article Mice Breast cancer Antigens CD Cell Line Tumor Internal medicine Receptors Transferrin medicine Animals Humans skin and connective tissue diseases Iron Regulatory Protein 2 Cell Proliferation Regulation of gene expression Gene knockdown Gene Expression Profiling Mammary Neoplasms Experimental Cancer medicine.disease Gene Expression Regulation Neoplastic Gene expression profiling Endocrinology Oncology Apoferritins Cancer cell Female Neoplasm Transplantation |
| Zdroj: | Cancer Research. 74:497-507 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-13-1224 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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