EIF5A2 is a novel chemoresistance gene in breast cancer

Breast Cancer. 2015 Nov;22(6):602-7. doi: 10.1007/s12282-014-0526-2. Epub 2014 Mar 18.

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.

Keywords: Breast cancer; Chemoresistance; Doxorubicin; eIF-5A2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor / drug effects
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm / genetics*
  • Eukaryotic Translation Initiation Factor 5A
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • MCF-7 Cells / drug effects
  • Peptide Initiation Factors / genetics*
  • Peptide Initiation Factors / metabolism
  • RNA, Small Interfering
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism

Substances

  • Antibiotics, Antineoplastic
  • Peptide Initiation Factors
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Doxorubicin