Yu Liu1, Feiya Du1, Wei Chen1, Minya Yao1, Kezhen Lv1, Peifen Fu2. 1. Breast Center of the First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China. 2. Breast Center of the First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China. peifenfu@163.com.
Abstract
BACKGROUND: The eIF5A2 gene (encoding the eukaryotic initiation factor 5A2) located at 3q26 is a putative oncogene that is overexpressed in colon and rectal carcinomas, lung cancer and hepatocellular carcinoma. EIF5A2 overexpression correlates significantly with tumor metastasis and is an adverse prognostic marker. However, eIF-5A2 overexpression in breast cancer and its effect on chemotherapy are unknown. METHODS: We measured eIF-5A2 expression and doxorubicin sensitivity in different human breast cancer cell lines (Bcap-1937, HCC1937, and MCF-7). To investigate a role for eIF-5A2 in chemoresistance, cells were treated with eIF-5A2-siRNA, exposed to various concentrations of doxorubicin, and toxicity was assayed by CCK-8 (cell counting kit). RESULTS: The eIF-5A2 expression levels varied among breast cancer cells. Higher expression levels correlated with decreased doxorubicin sensitivity. Silencing of eIF-5A2 significantly improved doxorubicin toxicity in all three breast cancer cell lines. CONCLUSION: This study shows that eIF-5A2 plays an important role in doxorubicin chemoresistance in breast cancer cells.
BACKGROUND: The eIF5A2 gene (encoding the eukaryotic initiation factor 5A2) located at 3q26 is a putative oncogene that is overexpressed in colon and rectal carcinomas, lung cancer and hepatocellular carcinoma. EIF5A2 overexpression correlates significantly with tumor metastasis and is an adverse prognostic marker. However, eIF-5A2 overexpression in breast cancer and its effect on chemotherapy are unknown. METHODS: We measured eIF-5A2 expression and doxorubicin sensitivity in different humanbreast cancer cell lines (Bcap-1937, HCC1937, and MCF-7). To investigate a role for eIF-5A2 in chemoresistance, cells were treated with eIF-5A2-siRNA, exposed to various concentrations of doxorubicin, and toxicity was assayed by CCK-8 (cell counting kit). RESULTS: The eIF-5A2 expression levels varied among breast cancer cells. Higher expression levels correlated with decreased doxorubicin sensitivity. Silencing of eIF-5A2 significantly improved doxorubicintoxicity in all three breast cancer cell lines. CONCLUSION: This study shows that eIF-5A2 plays an important role in doxorubicin chemoresistance in breast cancer cells.
Entities:
Keywords:
Breast cancer; Chemoresistance; Doxorubicin; eIF-5A2
Authors: Cynthia Bernier; Ahmed Soliman; Michel Gravel; Matthew Dankner; Paul Savage; Kevin Petrecca; Morag Park; Peter M Siegel; Gordon C Shore; Anne Roulston Journal: Anticancer Drugs Date: 2018-09 Impact factor: 2.248