Transcriptional regulation and biological functions of selenium-binding protein 1 in colorectal cancer in vitro and in nude mouse xenografts

PLoS One. 2009 Nov 16;4(11):e7774. doi: 10.1371/journal.pone.0007774.

Abstract

Background: It has been shown that selenium-binding protein 1 (SBP1) is significantly downregulated in different human cancers. Its regulation and function have not yet been established.

Methodology and principal findings: We show that the SBP1 promoter is hypermethylated in colon cancer tissues and human colon cancer cells. Treatment with 5'-Aza-2'-deoxycytidine leads to demethylation of the SBP1 promoter and to an increase of SBP1 promoter activity, rescues SBP1 mRNA and protein expression in human colon cancer cells. Additionally, overexpression of SBP1 sensitizes colon cancer cells to H2O2-induced apoptosis, inhibits cancer cell migration in vitro and inhibits tumor growth in nude mice.

Conclusion and significance: These data demonstrate that SBP1 has tumor suppressor functions that are inhibited in colorectal cancer through epigenetic silencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / genetics
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • DNA Methylation
  • Down-Regulation
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • In Vitro Techniques
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Promoter Regions, Genetic
  • Selenium-Binding Proteins / metabolism*

Substances

  • SELENBP1 protein, human
  • Selenium-Binding Proteins