Regulation of human growth and differentiation factor 3 gene expression by NANOG in human embryonic carcinoma NCCIT cells

FEBS Lett. 2012 Sep 21;586(19):3529-35. doi: 10.1016/j.febslet.2012.08.013. Epub 2012 Aug 19.

Abstract

We investigated transactivation by NANOG in regulating growth and differentiation factor 3 (GDF3) expression in NCCIT cells. GDF3 expression was affected by shRNA-mediated downregulation and by exogenous overexpression of NANOG specifically, as well as by retinoic acid-mediated differentiation. GDF3 transcription was activated by NANOG, and the upstream region (-183 to -1) was sufficient to induce minimal transcriptional activity. Moreover, NANOG binds to the GDF3 minimal promoter in vivo and the transcriptional activity is mediated by NANOG transactivation domain. This study provides the first evidence that NANOG is a transcriptional activator of the expression of the oncogenic growth factor GDF3 in embryonic carcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites / genetics
  • Carcinoma, Embryonal / genetics*
  • Carcinoma, Embryonal / metabolism*
  • Carcinoma, Embryonal / pathology
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Growth Differentiation Factor 3 / genetics*
  • HEK293 Cells
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Nanog Homeobox Protein
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Pluripotent Stem Cells / metabolism
  • Pluripotent Stem Cells / pathology
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • RNA, Small Interfering / genetics
  • Sequence Homology, Nucleic Acid
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Tretinoin / pharmacology

Substances

  • GDF3 protein, human
  • Growth Differentiation Factor 3
  • Homeodomain Proteins
  • NANOG protein, human
  • Nanog Homeobox Protein
  • RNA, Small Interfering
  • Trans-Activators
  • Tretinoin