C/EBPα inactivation in FAK-overexpressed HL-60 cells impairs cell differentiation

Ken Ichiro Hashimoto, Yoshiko Sonoda, Masakazu Yamakado, Megumi Funakoshi-Tago, Naomi Yoshida, Akiko Rokudai, Eriko Aizu-Yokota, Tadashi Kasahara

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We previously demonstrated that focal adhesion kinase (FAK)-overexpressed (HL-60/FAK) cells have marked resistance against various apoptotic stimuli such as oxidative stress, ionizing radiation and TNF-receptor-induced ligand (TRAIL) compared with vector-transfected (HL-60/Vect) cells. Here, we show that HL-60/FAK cells are highly resistant to all-trans retinoic acid (ATRA)-induced differentiation, whereas original HL-60 or HL-60/Vect cells are sensitive. Treatment with ATRA at 1 μM for 5 days markedly inhibited the proliferation and increased the expression of differentiation markers (CD38, CD11b) in HL-60/Vect cells, but showed no such effect in HL-60/FAK cells. Electrophoretic mobility shift assay (EMSA) using an oligonucleotide for the c/EBP consensus binding sequence showed that c/EBPα was activated in ATRA-treated HL-60/Vect cells but not in HL-60/FAK cells, indicating that c/EBPα activation by ATRA was impaired in HL-60/FAK cells. In addition, the association of retinoblastoma protein (pRb) and c/EBPα after treatment with ATRA was seen in HL-60/Vect cells but not in HL-60/FAK cells. Further, hyperphosphorylation of pRb was observed in HL-60/FAK cells. Finally, the introduction of FAK siRNA into HL-60/FAK cells resulted in the recovery of sensitivity to ATRA-induced differentiation, confirming that the inhibition of HL-60/FAK differentiation resulted from both the induction of pRb hyperphosphorylation and the inhibition of association of pRb and c/EBPα.

Original languageEnglish
Pages (from-to)955-963
Number of pages9
JournalCellular Signalling
Volume18
Issue number7
DOIs
Publication statusPublished - 2006 Jul 1

Keywords

  • Differentiation
  • FAK
  • Granulocyte
  • c/EBP
  • pRb

ASJC Scopus subject areas

  • Cell Biology

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