Altered mouse mammary gland gene expression and tumor growth following chronic social isolation

Clinical studies have revealed that social support improves the outcome of cancer patients while epidemiological studies suggest that social isolation increases the risk of death associated with several chronic diseases. However, the precise biological consequences of an unfavorable social environment have not been defined. To do so, robust, reproducible pre-clinical models are needed to study the mechanisms whereby an adverse environment impacts on 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 pre-clinical 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 upregulated fatty acid synthesis and glycolytic pathway gene expression - both pathways known to contribute to increased breast cancer growth. Consistent with the expression of metabolic genes, isolated mice subsequently developed significantly larger mammary gland tumors compared to group-housed mice. Endocrine evaluation confirmed that isolated mice developed a heightened corticosterone stress response compared to 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 favoring tumor growth suggests potential molecular biomarkers and/or targets (e.g. fatty acid synthesis) for preventive intervention in breast cancer.

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