Effect of social housing condition on heat shock protein (HSP) expression in the Shionogi mouse mammary carcinoma (SC115).

Our previous studies have shown that social housing conditions can significantly alter the growth rate of the Shionogi mouse mammary carcinoma (SC115). The present study extended our investigations to the molecular level by examining stressor effects on the expression of a group of stress-responsive proteins, the heat shock proteins (HSPs). We hypothesized that HSP expression in SC115 cells may be altered by (a) different social housing conditions in vivo and (b) steroid hormone and growth factor exposure in vitro. Mice were reared in groups (G) or as individuals (I). Immediately following tumor cell injection, mice were rehoused from group to individual (GI), from individual to group (IG), or they remained in groups (GG). Tumor tissue was resected at 0.8 g or 3.0 g, as evidence suggests that tumor size affects HSP expression, which in turn affects proliferation. The data demonstrate that expression of HSP25, 70, and 90 was increased in tumors from mice in the IG compared to GG and GI mice, at both tumor weights examined. In addition, in IG mice, HSP90 expression was greater in 0.8 g compared to 3.0 g tumors. Under controlled culture conditions, hormones known to stimulate SC115 growth both in vivo and in vitro altered HSP expression. Physiological levels of dihydrotestosterone (DHT) and pharmacological levels of hydrocortisone (HC) upregulated expression of HSP25, whereas physiological levels of beta-estradiol (E2) upregulated expression of HSP90. These data are the first to demonstrate that a psychosocial stressor, a change in social housing condition, can induce differential HSP expression. Further, these data show that hormones that regulate SC115 tumor growth, also alter HSP expression.

Psychosocial stressors and mammary tumor growth: an animal model.

Stressful life events and the ability to cope with stress may play a role in the progression of breast cancer; however, the complex relationship between stressors and tumor growth is difficult to investigate in humans. Our studies have utilized the androgen-responsive Shionogi mouse mammary carcinoma (AR SC115) in male mice to investigate the effects of social housing condition on tumor growth rates and responses to chemotherapy. We demonstrate that, depending on social housing condition, mammary tumor growth and response to chemotherapy can both increase and decrease. We have examined the possible role(s) of 1) psychosocial variables, 2) testosterone and corticosterone, hormones altered by stress and known to stimulate SC115 cells in vivo and in vitro, 3) NK cells, one of the body's first lines of defense against tumor cells, 4) stress proteins, in mediating the differential tumor growth rates observed in our model. This review discusses the investigations we have undertaken to elucidate the mechanisms through which a psychosocial stressor, social housing condition, can alter tumor growth rate.

Exercise during puberty and NMU induced mammary tumorigenesis in rats.

Previously we have shown that exercising rats prior to administration of 50 mg NMU/kg (high dose) significantly decreased tumor multiplicity, but not incidence or latency. We hypothesized that the dose of NMU saturated the system such that the exercise intervention was overshadowed. Therefore, the purpose of this investigation was to determine if exercise would have a more pronounced effect with a moderate dose of 37.5 mg NMU/kg. Female Sprague Dawley rats were divided into sedentary and exercised groups. The rats were exercised five times per week from 21 to 50 days of age on a progressive treadmill training program with a final workload of 18 m/min at 15% incline for 60 min a day. At 50 days of age all rats were given an i.p. injection of NMU at 37.5 mg/kg body weight. The experiment was terminated 22 weeks post carcinogen administration. Although there was no difference in terms of tumor incidence, multiplicity, or latency between the two groups, the tumor growth rate (0.107+/-0.025 vs. 0.043+/-0.009 g/day) and final tumor weight (3.2+/-0.74 vs. 1.2+/-0.34 grams) were significantly higher in the exercised animals. IGF-I receptor (9.4+/-96 vs. 10.5+/-57 per microg protein) and estrogen receptor (18.4+/-1.14 vs. 19.6 + 1.6 per microg protein) levels were not significantly different in tumors from exercised animals compared to those from sedentary animals. For both sets of tumors, correlation between estrogen receptor content and growth rate is positive, while the correlation between IGF-I receptor content and growth rate is negative. The results of this study suggest that exercise prior to NMU administration does not affect tumor burden but does alter tumor growth rate, which is not due to differences in estrogen receptor or IGF-I receptor content.