Shc proteins in DMBA induced breast cancer

The principal factors that control mammary tumor formation remain insufficiently defined. Shc adaptor proteins play an important role in signaling by three well-established biological markers for prognosis and response to breast cancer therapy (epidermal growth factor receptor-2, estrogen receptor and prolactin signaling), but the role of individual Shc proteins (p52Shc and p66Shc) in mammary tumor progression remains unknown. This project aims to uncover the mechanisms of mammary tumor progression. We hypothesize that Shc proteins are crucial regulators of the progression of breast cancer. Using genetically modified rats, which we have generated using targeted genome-editing techniques, we address for the first time the role of p66Shc and p52Shc isoforms in the progression of mammary carcinomas. These rats lack either p52Shc (p52ShcKO), or p66Shc (p66ShcKO). RNAseq analysis of mammary tumors formed in wild type and genetically modified rats provides rationale for studying signaling cascades, previously unknown to be regulated by Shc proteins, as a potential therapeutic target for breast cancer treatment.