Abstract 3493: Promoting role of AKR1B10 in HER2+ breast cancer at early stage

Abstract

Abstract Background: Breast cancer is the second most common cause of female cancer-related death in the United States. Aldo-keto reductase 1B10 (AKR1B10) is a 35-kDa protein that is highly expressed in breast cancer in infiltrative and Ductal Carcinoma in Situ (DCIS) stages. Human epidermal growth factor receptor2 (HER2) is a tyrosine kinase receptor which is highly expressed in 15-20% of infiltrative breast cancer but over 60-70 % in DCIS. Methods: We targeted AKR1B10 and HER2 expression using AKR1B10 and HER2 expression lentiviruses in a panel of breast cancer cell lines that have different endogenous expression status of AKR1B10 or HER2, including MCF-7(AKR1B10-/HER2 low), ZR-75-1(AKR1B10-/HER2+), MDA-MB-468 (AKR1B10+/HER2-) and the normal human mammary cells MCF10A (AKR1B10-/HER2-). We investigated the effects of AKR1B10 or HER2 expression on cell proliferation, clonogenicity, adhesion, migration, and invasion. Western blots were performed to check integrin α5, δ-catenin expression and the phosphorylation of signaling proteins in Raf/MEK/ERK and AKT/P-mTOR pathways. Results: Our data showed that AKR1B10 promoted the proliferation of HER2+ human breast cancer cell. The results of colony forming and soft agar assays demonstrated that AKR1B10 stimulated clonogenic efficiency of HER2+ cells. Also, AKR1B10 promoted HER2+ cells adhesion to extracellular matrix, facilitated their migration and significantly increased their invasion capability. Moreover, it upregulated integrin α5, δ-catenin expression, and promoted HER2+ cells growth and invasiveness through the activation of AKT/mTOR and Raf/MEK/ERK pathways Conclusion: AKR1B10 promotes HER2+ human breast cancer cell proliferation and invasiveness. Citation Format: Ramina Khoshaba, Deliang Cao. Promoting role of AKR1B10 in HER2+ breast cancer at early stage [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3493.