The Involvement of Human Cyr61 in Heregulin Induction of Breast Tumor Progression
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This fellowship, originally granted to Dr. M. Tsai and later transferred to Dr. H. Oketch-Rabah in the laboratory of Dr. R. Lupu, was initially concerned with the role of the cytokine heregulin, in the regulation of hormone receptor status in breast cancer. Three projects were accomplished during the fellowship. The first based on the original SOW yielded information that demonstrated that Cyr61 is a downstream effector of Heregulin (HRG) action and suggested that Cyr61 is necessary for HRG- mediated chemomigration. Furthermore the work showed that Cyr61 plays a functional role in breast cancer progression, possibly through its interactions with the alpha(v)beta3 receptor (see attached publications). The findings of Dr. Oketch-Rabab on the Black Cohosh project demonstrated that BC has no estrogenic activity and therefore is safe to use for the treatment of menopausal symptoms by women at risk of developing breast cancer and in whom estrogen replacement therapy is contraindicated for other reasons (see attached Abstracts). In the final year we requested a modified SOW due to Dr. Lupu's relocation. Dr. Oketch-Rabah began a project in the Barcellos-Hoff laboratory to examine TGF-(beta)1 regulation of the proliferation of estrogen receptor positive (ER+) cells during mouse mammary development. To our knowledge this is the first mouse model to demonstrate a mechanism controlling the size of the ER+ subpopulation and a means of investigating how the dysregulation of this population contributes to the risk of developing breast cancer.