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Neuregulin 1-HER axis as a key mediator of hyperglycemic memory effects in breast cancer
- Park, Jiyoung, Sarode, Venetia R., Euhus, David, Kittler, Ralf, Scherer, Philipp E.
- Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.51 pp. 21058-21063
- breast neoplasms, chromatin, diabetes, gene expression, genes, humans, hyperglycemia, messenger RNA, neoplasm cells, patients
- 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.