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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Breast Neoplasms / complications
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Breast Neoplasms / metabolism
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CHO Cells
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Cell Line, Tumor
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Cell Proliferation
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Cricetinae
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Diabetes Mellitus / metabolism*
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Epigenesis, Genetic
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Gene Expression Regulation*
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Genomic Imprinting
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HEK293 Cells
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Humans
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Hyperglycemia / complications
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Hyperglycemia / metabolism
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Mice
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Neuregulin-1 / metabolism*
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Oligonucleotide Array Sequence Analysis
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RNA, Messenger / metabolism
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Receptor, ErbB-3 / metabolism*
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Signal Transduction
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Tumor Cells, Cultured
Substances
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Neuregulin-1
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RNA, Messenger
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Receptor, ErbB-3
Associated data
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GEO/GSE40361
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GEO/GSE40949