Reduced selenium-binding protein 1 in breast cancer correlates with poor survival and resistance to the anti-proliferative effects of selenium

PLoS One. 2013 May 21;8(5):e63702. doi: 10.1371/journal.pone.0063702. Print 2013.

Abstract

Supplemental dietary selenium is associated with reduced incidence of many cancers. The antitumor function of selenium is thought to be mediated through selenium-binding protein 1 (SELENBP1). However, the significance of SELENBP1 expression in breast cancer is still largely unknown. A total of 95 normal and tumor tissues assay and 12 breast cancer cell lines were used in this study. We found that SELENBP1 expression in breast cancer tissues is reduced compared to normal control. Low SELENBP1 expression in ER(+) breast cancer patients was significantly associated with poor survival (p<0.01), and SELENBP1 levels progressively decreased with advancing clinical stages of breast cancer. 17-β estradiol (E2) treatment of high SELENBP1-expressing ER(+) cell lines led to a down-regulation of SELENBP1, a result that did not occur in ER(-) cell lines. However, after ectopic expression of ER in an originally ER(-) cell line, down-regulation of SELENBP1 upon E2 treatment was observed. In addition, selenium treatment resulted in reduced cell proliferation in endogenous SELENBP1 high cells; however, after knocking-down SELENBP1, we observed no significant reduction in cell proliferation. Similarly, selenium has no effect on inhibition of cell proliferation in low endogenous SELENBP1 cells, but the inhibitory effect is regained following ectopic SELENBP1 expression. Furthermore, E2 treatment of an ER silenced high endogenous SELENBP1 expressing cell line showed no abolishment of cell proliferation inhibition upon selenium treatment. These data indicate that SELENBP1 expression is regulated via estrogen and that the cell proliferation inhibition effect of selenium treatment is dependent on the high level of SELENBP1 expression. Therefore, the expression level of SELENBP1 could be an important marker for predicting survival and effectiveness of selenium supplementation in breast cancer. This is the first study to reveal the importance of monitoring SELENBP1 expression as a potential biomarker in contributing to breast cancer prevention and treatment.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Drug Resistance, Neoplasm / drug effects*
  • Estrogens / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Neoplasm Staging
  • Organoselenium Compounds / pharmacology
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Selenium / pharmacology*
  • Selenium-Binding Proteins / genetics
  • Selenium-Binding Proteins / metabolism*
  • Survival Analysis
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Estrogens
  • Organoselenium Compounds
  • Receptors, Estrogen
  • Receptors, Progesterone
  • SELENBP1 protein, human
  • Selenium-Binding Proteins
  • Tumor Suppressor Protein p53
  • methylselenic acid
  • Selenium

Grant support

The authors have no support or funding to report.