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UBC Theses and Dissertations

Heat shock protein (HSP) expression in the shionogi mouse mammary carcinoma (SC115) in response to steroid hormone treatment in vitro and a change in social housing conditions in vivo Andrews, Heather Nicola


Previous studies in our laboraotry have shown that social housing conditions can significantly alter the growth rate of the Shionogi mammary carcinoma (SC115). The present study extended investigations of mechanisms underlying the effects of housing condition on tumor growth rate. We focused on changes occurring at the molecular level, on the expression of a group of stress-responsive proteins, the heat shock proteins (HSPs). HSP25, 70 and 90 were examined in SC115 cells in vitro, following exposure to SC115 growth regulatory hormones, and in tumors grown in vivo in mice in different social housing conditions. In vitro, physiological levels of dihydrotestosterone (DHT, n=3) and pharmacological levels of hydrocortisone (HC, n=3) upregulated HSP25, whereas HSP70 and 90 remained unchanged. Conversely, physiological levels of β-estradiol (E₂, n=2) upregulated HSP90, whereas HSP25 and 70 remained unchanged. For the in vivo experiments, mice were reared in groups (G) or as individuals (I). Immediately following tumor cell injection, mice were rehoused from group to individual (Gl, n=36), from individual to group (IG, n=40) or they remained in groups (GG, n=36). All animals (Gl, GG, IG, n=112) were exposed to a daily novelty stressor, shown to increase the differences in tumor growth rates among mice in the different social housing conditions. In addition, mice in a control condition were maintained under standard housing conditions (no housing change or daily novelty stress, GGNS, n=12). Tumor tissue was resected for HSP examination when the average weight of tumors reached 0.8 g (n=56) or 3 g (n=56). In mice subjected to daily novelty stress, HSP25, 70 and 90 was increased in tumors from IG mice compared to GG and Gl mice (0.8 g and 3 g tumors). HSP90 was greater in 3 g tumors compared to 0.8 g tumors from mice in the IG condition. In group housed mice (GGNS and GGS), daily novelty stress decreased HSP70 (0.8 g and 3 g tumors), decreased HSP90 (3 g tumors), and did not alter HSP25. This study has shown that HSP expression is altered in SC115 cells by steroid hormones in vitro and this is the first study to report that psychosocial stressors, a change in social housing condition, can also induce differences in HSP expression in vivo.

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