Pin1 as a Biomarker of ER+ Breast Cancers to Predict the Response to Tamoxifen and mTOR Inhibitors

摘要

Previous work in our lab suggested a role for Pin1 in modulating LPS- stimulated IL-6 mRNA accumulation and protein secretion. We utilized primary Pin1 null MEFs to investigate the mechanism by which Pin1 modulates IL-6 production. We then aimed to determine a role for Pin1 (via regulation of IL-6 production) in modulating the sensitivity of breast cancer cells to chemotherapeutic agents. Our experiments, however, failed to produce reliable and convincing data to support a role for Pin1 in IL-6 production. Because of these results, we turned our attention to the observed in vivo inflammatory defects in our Pin1 null mice. We currently have evidence to support a role for Pin1 in modulating in vivo splenic Dendritic cell (DC) accumulation and ex vivo DC differentiation. Additionally, we find an elevation in the number of splenic Mac1+ granular cells in Pin1 null mice. Tumor-induced immunosuppression is a well-documented phenomenon, and is often associated with decreased numbers of circulating DC and increased numbers of circulating Mac1+ granular Myeloid- Derived Suppressor Cells (MDSC). For these reasons, we are interested in determining the ability of Pin1 null DC and Mac1+ granular cells to influence T cell function. We will also utilize a mouse model of mammary carcinoma to determine whether absence of Pin1 creates a more tumorpermissive immune environment for breast cancer growth.