Stressful life events and the ability to cope with stress may play a role the progression of breast cancer, but this complex relationship is difficult to investigate in humans. The investigators' studies using the androgen-responsive Shionogi mouse mammary carcinoma (AR SC115) in male mice have demonstrated dramatic effects of social housing condition on tumor growth rates and responses to chemotherapy. Data suggest that both endocrine and immune variables may be involved in mediating these effects. This application will focus on endocrine factors, utilizing 2 animal-tumor models. The first involves the AR SC115 tumor. Although this model utilizes male mice, the sensitivity of this tumor to steroid hormones has analogies to human breast cancer. The second involves a variant of the AR SC115 tumor (SC115V, recently developed in the investigators' laboratory) that grows equally well in both females and males and responds similarly to the AR SC115 tumor to social housing conditions. The second model provides a means of studying the interactive effects of psychosocial stressors and both the female and male hormonal environments on growth of the same mammary tumor. The working hypothesis in this application is that the effects of stressors on tumor growth are mediated through changes in hormonal activity that either directly affect the tumor itself or act indirectly by altering immunocompetence.
The specific aims are to determine: 1) the role of specific endocrine factors in mediating the effects of psychosocial stressors on tumor growth rate in the AR SC115 tumor in male mice; 2) if stress-induced changes in the endocrine system result in either different stress proteins or different levels of a specific stress protein(s) in the AR SC115 tumor, which in turn may influence tumor growth rates; 3) if stress-induced alterations in responsiveness of the AR SC115 tumor to chemotherapy occur regardless of tumor burden and tumor growth rate; and 4) the role of specific endocrine factors in mediating the effects of psychosocial stressors in the SC115V tumor in both female and male mice. These studies aim to help elucidate the factors that may influence the course of breast cancer, which is essential for the development of improved prevention and treatment strategies.
| Kerr, Leslie R; Andrews, Heather N; Strange, Karen S et al. (2006) Temporal factors alter effects of social housing conditions on responses to chemotherapy and hormone levels in a Shionogi mammary tumor model. Psychosom Med 68:966-75 |
| Kerr, L R; Hundal, R; Silva, W A et al. (2001) Effects of social housing condition on chemotherapeutic efficacy in a Shionogi carcinoma (SC115) mouse tumor model: influences of temporal factors, tumor size, and tumor growth rate. Psychosom Med 63:973-84 |
| Andrews, H N; Kerr, L R; Strange, K S et al. (2000) Effect of social housing condition on heat shock protein (HSP) expression in the Shionogi mouse mammary carcinoma (SC115). Breast Cancer Res Treat 59:199-209 |
| Kerr, L R; Wilkinson, D A; Emerman, J T et al. (1999) Interactive effects of psychosocial stressors and gender on mouse mammary tumor growth. Physiol Behav 66:277-84 |
