Abstract:
Breast cancer (BRCA) is the most frequently diagnosed cancer in females over the world. HER2-positive (HER2+) breast cancer accounts for 15%~20% of total breast cancer, which related to HER2 overexpression and rapid deteriorations of cancer. Lapatinib is a dual EGFR/HER2 inhibitor for HER2+ breast cancer therapy, while the drug resistance is the main reason for treatment failure. As a critical component of the translational machinery, eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) was significantly upregulated to promote the cancer progression in various tumors like breast tumor. This study explored the potential relation of EEF1A2 and HER2 in breast cancer. The
EEF1A2 mRNA expressions in human breast cancer tissues were analyzed by TCGA online data. The differences of
EEF1A2 mRNA levels and its impacts to prognosis between HER2-positive breast cancer tissues and HER2-negative ones were further detected. The EEF1A2-knockdown plasmid was constructed via shRNA for the further transfection. Subsequently, we explored the proliferation, metastasis and apoptosis of SKBR3 and MDA-MB-453, the HER2-positive breast cancer cells, treated with EEF1A2-knockdown and lapatinib via MTT, colony formation, transwell assay and apoptosis assay, respectively. Results of TCGA analysis showed that
EEF1A2 mRNA overexpressed in breast cancer tissues. Most importantly, the level of
EEF1A2 mRNA in HER2-positive breast cancer tissues was significantly higher than that in HER2-negative subtype. The higher level of
EEF1A2 mRNA correlated with the lower overall survival in HER2-positive breast cancer. While the EEF1A2-knockdown enhanced the lapatinib’s impacts on proliferation, migration, invasion and apoptosis of SKBR3 and MDA-MB-453
in vitro. Western blot showed the EEF1A2-knockdown augmented the inhibition on HER2/AKT pathway induced by lapatinib in cells. Thus, we suggested that EEF1A2 could be a potential target to improve the therapy of HER2-positive breast cancer treated with lapatinib.