19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)21058-21063
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number51
DOIs
StatePublished - Dec 18 2012

Fingerprint

Neuregulin-1
Breast Neoplasms
Neoplasms
Chromosome Mapping
Hyperglycemia
Chromatin
Ligands
Messenger RNA
Growth
Genes

Keywords

  • FAIRE-seq
  • Metabolic imprinting
  • PANIC-ATTAC

ASJC Scopus subject areas

  • General

Cite this

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title = "Neuregulin 1-HER axis as a key mediator of hyperglycemic memory effects in breast cancer",
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.",
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author = "Jiyoung Park and Sarode, {Venetia R.} and David Euhus and Ralf Kittler and Scherer, {Philipp E.}",
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T1 - Neuregulin 1-HER axis as a key mediator of hyperglycemic memory effects in breast cancer

AU - Park, Jiyoung

AU - Sarode, Venetia R.

AU - Euhus, David

AU - Kittler, Ralf

AU - Scherer, Philipp E.

PY - 2012/12/18

Y1 - 2012/12/18

N2 - 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.

AB - 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.

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KW - Metabolic imprinting

KW - PANIC-ATTAC

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