A model of gene-environment interaction reveals altered mammary gland gene expression and increased tumor growth following social isolation

J. Bradley Williams, Diana Pang, Bertha Delgado, Masha Kocherginsky, Maria Tretiakova, Thomas Krausz, Deng Pan, Jane He, Martha K. McClintock, Suzanne D. Conzen

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Clinical studies have revealed that social support improves the outcome of cancer pa-tients, whereas epidemiologic studies suggest that social isolation increases the risk of death associated with several chronic diseases. However, the precise molecular consequences of an unfavorable social environment have not been defined. To do so, robust, reproducible preclinical models are needed to study the mechanisms whereby an adverse environment affects gene expression and cancer biology. Because random assignment of inbred laboratory mice to well-defined social environments allows accurate and repeated measurements of behavioral and endocrine parameters, transgenic mice provide a preclinical framework with which to begin to determine gene-environment mechanisms. In this study, we found that female C3(1)/SV40 T-antigen mice deprived of social interaction from weaning exhibited increased expression of genes encoding key metabolic pathway enzymes in the pre-malignant mammary gland. Chronic social isolation was associated with up-regulated lipid synthesis and glycolytic pathway gene expression - both pathways are known to contribute to increased breast cancer growth. Consistent with the expression of metabolic genes in pre-malignant mammary tissue, isolated mice subsequently developed a significantly larger mammary gland tumors burden compared with group-housed mice. Endocrine evaluation confirmed that isolated mice developed a heightened corticosterone stress response compared with group-housed mice. Together, these transdisciplinary studies show for the first time that an adverse social environment is associated with altered mammary gland gene expression and tumor growth. Moreover, the identification of specific alterations in metabolic pathways gene expression favoring tumor growth suggests potential molecular biomarkers and/or targets (e.g., fatty acid synthesis) for preventive intervention in breast cancer.

Original languageEnglish (US)
Pages (from-to)850-861
Number of pages12
JournalCancer Prevention Research
Volume2
Issue number10
DOIs
StatePublished - Oct 1 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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