Abstract SY04-02: Environmental stress and breast cancer biology: What is the link

Abstract

Abstract For many decades, identifying neuroendocrine mechanisms linking psychosocial factors (e.g., chronic stressors) to human disease has been the subject of intense interest by both social and biological scientists. Together, the endocrine and autonomic nervous systems comprise an individual's physiological response to both chronic and acute social stressors; these systems also mediate signaling pathways and gene expression changes at the cellular level that have the potential to alter tumor biology. However, it is only recently that the detailed molecular components connecting biopsychological stressors and cancer biology have begun to be uncovered. For example, in preclinical models of both breast and ovarian cancer, there is growing evidence linking biopsychological stressors and ensuing changes in neuroendocrine dynamics to the promotion of tumor growth. Both the glucocorticoid stress hormones and the adrenergic systems can induce tumor cell survival mechanisms and alter cell proliferation, tumor invasion, and angiogenesis. In addition, these signals affect inflammatory and metabolic tissues that modulate tumor growth through systemic and microenvironmental effects. Assessing the precise mechanisms of these interactions requires an appreciation of the subtleties of measuring the social environment, the individual's behavioral and neuroendocrine response, as well as the tumor and its environment. Our collaborative development of a model of social isolation as it pertains to a transgenic model of human breast cancer (SV40Tag) and a Sprague-Dawley female rat model of spontaneous mammary gland cancer will be presented. In both models, we found that chronic social isolation reduces exploratory behavior in a novel environment as well as heightening the corticosterone response to an acute restraint stressor. In the SV40 Tag model, we examined gene expression differences in the mammary glands of isolated versus grouped female mice prior to invasive tumor development and uncovered a significant increase in lipid synthesis and glycolytic pathway genes, suggesting an association of the social environment with cancer-promoting metabolic changes. Interestingly, many of these changes in gene expression appear most significant in the adipocyte fraction of the mammary gland. For example, the increased expression of the key metabolic genes Acaca, Hk2, and Acly, initially observed in the whole mammary gland, was found to be significantly elevated only in the adipocyte fraction. Furthermore, metabolic gene expression was not consistently increased in the visceral fat of social isolates. These results suggest that exposure to chronic social isolation results in mammary fat depot-specific metabolic gene expression changes, followed by increased growth of invasive tumors. The implications and limitations of these two breast cancer models – one transgenic and one spontaneous – will be discussed in the context of understanding specific mechanisms that confer increased nonestrogen-dependent mammary tumor growth in association with chronic exposure to a psychosocial stressor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY04-02. doi:10.1158/1538-7445.AM2011-SY04-02