The Role of IQGAP1 in Breast Carcinoma
Annual summary rept. 15 Sep 2009-14 Sep 2010
BRIGHAM AND WOMENS HOSPITAL BOSTON MA
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HER2 is overexpressed in 25 of breast carcinomas. Overexpression of HER2 is an adverse prognostic feature and correlates with shorter disease-free and overall survival. HER2 breast cancer is treated with trastuzumab but many patients do not respond. Of those who do, most become refractory to therapy and progress to metastatic disease. An insight into the molecular mechanisms underlying HER2 signaling and trastuzumab resistance is essential to reduce breast cancer morbidity and mortality. IQGAP1 is a ubiquitously expressed scaffold protein that contains multiple protein interaction domains. Through interaction with its binding partners, IQGAP1 integrates diverse signaling pathways, several of which are relevant to breast tumorigenesis. The purpose of this proposal is to elucidate the function of selected IQGAP1 binding interactions in breast neoplasia. During Year 1 of this fellowship, we have shown that IQGAP1 interacts with HER2 in vitro and in a normal cellular milieu. Furthermore, IQGAP1 and HER2 co-immunoprecipitate from SkBR3 cells. The remainder of this award will be spent evaluating the functional consequences of this interaction on HER2 signaling and trastuzumab resistance. Elucidation of the molecular mechanism underpinning this interaction could potentially lead to the development of novel and specific therapeutic agents for the treatment of patients with HER2 breast cancer.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research