Aldo-keto Reductase Family 1 B10 as a Novel Target for Breast Cancer Treatment

摘要

Breast cancer is the most common carcinoma of women in the United States, accounting for more than 40,000 American women's deaths annually. Targeted therapies, such as tamoxifen in estrogen receptor-positive breast cancer, have led to major important improvements in the outcomes of this cancer, but effective chemotherapy targets are lacking and the mortality rate of advanced breast cancer is still high. Aldo-keto reductase 1 B10 (AKR1B10) is overexpressed in tested human breast cancer tissues and mediates acetyl-CoA carboxylase-alpha (ACCA) stability, affecting fatty acid de novo synthesis and cell growth. This study is aimed to identify and evaluate AKR1B10 as a now target for the treatment of breast cancer. In this study, we will determine AKR1B10 expression in breast cancer, define the role of AKR1B10 in lipid metabolism, proliferation, and tumorigenicity of breast cancer cells using AKR1B10-targeted breast cancer cells and animal tumor models, and elucidate the regulatory mechanisms of AKR1B10 on lipid metabolism of breast cancer cells via identifying the functional domain(s).