127P - Studies on the carcinogenic mechanisms of Growth Receptor Bound Protein 7 in breast cancer cells and its clinical therapeutic applications

Abstract

Background: Growth factor receptor bound protein 7 (GRB7) is a member of Grb family, and it is an adaptor protein. GRB7 has five functional domains, participated in many different signaling pathway.Human epidermal growth factor receptor 2 (HER2) is classified as a subtype in breast cancer. Studies until now have indicated that GRB7 and HER2 are highly correlated. Methods: To further confirm the relationship between GRB7 and HER2, GRB7 mRNA and protein levels were analyzed in different breast cancer cell lines and clinical patients tissue (N = 213). Results: We found that GRB7 highly expressed in HER2 positive breast cancer cell lines and HER2 positive patients’ tissues. GRB7 definitely existed in cytosol and nucleus in SKBR3 breast cancer cell, but GRB7 could not regulate HER2 gene expression directly. In addition, we constructed the knocked down GRB7 plasmid and overexpression GRB7 plasmid. We proved that HER2 would decrease when we knocked down GRB7; HER2 protein level would not change when we overexpressed GRB7.Utilizing a nature compound named curcumin to treat SKBR3 cells decreased GRB7 protein expression. Further analysis using cycloheximide to identify the possible degradation mechanism of GRB7, and the consequence indicated that GRB7 protein was directed to the path of hydrolysis, rather than being inhibited during the synthesis. Conclusions: By inhibiting GRB7 and can decrease the excessive expression of HER2. These results imply that GRB7 could be a potential molecule for therapy and prognosis prediction in breast cancer patients. Legal entity responsible for the study: N/A Funding: This study was supported by the Ministry of Science and Technology, Taiwan (MOST 106-2320-B-038-061 -MY3). Disclosure: The author has declared no conflicts of interest.