Modification of TGF-beta1 signaling pathway during NB4 cells differentiation by all-trans retinoid acid induction

Int J Hematol. 2009 May;89(4):438-444. doi: 10.1007/s12185-009-0293-6. Epub 2009 Apr 14.

Abstract

The aim of the study was to present the possible mechanisms of transforming growth factor beta 1(TGF-beta1) signal pathway during cell differentiation by studying the expression levels of six components of TGF-beta1 pathway (TGF-beta1, two TGF-beta1 receptors and three Smad proteins). The morphology change, the CD11 expression levels, and the mRNA and protein expression levels of TGF-beta1, TGF-beta ReceptorI (TbetaRI), TGF-beta ReceptorII (TbetaRII), Smad2, Smad4 and Smad7 were assessed by exposing NB4 cells to all-trans retinoid acid (ATRA) using Wright's stain, flow cytometry, real-time PCR assay and Western blot analysis. The mRNA and protein expression levels of all six components increased during NB4 cells differentiation induced by ATRA. They were most significantly increased after 24-72 h individually when cells were induced by ATRA (the mRNA and protein expression levels of TGF-beta1, TbetaRI, TbetaRII and Smad2 reached their peaks at 48 and 48 h individually after the treatment, Smad4 at 48 and 72 h, and Smad7 at 72 and 72 h). The change in mRNA expression levels was earlier than the change in the same gene controlling protein. These results indicate that the upregulation of TGF-beta1 pathway plays an important role in NB4 cells differentiation induced by ATRA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Humans
  • RNA, Messenger / genetics
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction / drug effects*
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*
  • Tretinoin / pharmacology*

Substances

  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Smad Proteins
  • Transforming Growth Factor beta1
  • Tretinoin