A mouse model of breast cancer reveals social environment-tumor interactions Free

CN05-02

Background: The psychosocial environment exerts potentially powerful effects on physical health. Research in our laboratories now demonstrates that the psychosocial environment modulates development of mammary gland cancer. Objective: The main goal of our studies is to determine whether psychosocial factors influence breast tumor biology and if so, to characterize the physiological and molecular mechanisms through which these environmental factors act. Through a cross-disciplinary collaboration, we are examining the effects of social isolation on the acute corticosterone stress response and the mechanisms whereby altered corticosterone responses to everyday stressors affect mammary gland cancer. In humans it is nearly impossible to chart the lasting impact of early psychosocial influences on distant pathological outcomes. Moreover, the inability to randomly assign social conditions precludes moving beyond correlational studies. In contrast, animal models allow one to observe how psychosocial events change physiology and in turn, gene expression and ultimately, tumor development.
 Methods: We are using the mammary epithelial cell-targeted SV40 T antigen (SV40-Tag) transgenic mouse to assess whether mammary gland carcinomas can be influenced by psychosocial events. This research is uncovering the neuroendocrine correlates of the social environment and connecting physiological changes with mammary gland carcinogenesis. Results: Our data show that SV40 Tag mice placed in social isolation from weaning develop a greater corticosterone response to a moderate stressor (30 minute restraint). Overall tumor incidence and tumor volume is higher in socially isolated versus group-housed mice. We have also found that lifelong social isolation increases vigilant behavior, raising the possibility that this behavior and its associated physiological state may mediate the link between social isolation and mammary gland biology. Behavioral testing and endocrine measurements, as well as molecular/pathological characterization of mammary tumors including gene expression differences will be presented. Conclusions: These studies allow a cross-disciplinary analysis of psychosocial factors and the physiological mechanisms by which these factors may affect the biology of mammary epithelial cell growth and tumorigenesis.