C/EBPalpha inactivation in FAK-overexpressed HL-60 cells impairs cell differentiation
| Autor: | Ken Ichiro Hashimoto, Naomi Yoshida, Tadashi Kasahara, Yoshiko Sonoda, Megumi Funakoshi-Tago, Akiko Rokudai, Masakazu Yamakado, Eriko Aizu-Yokota |
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| Rok vydání: | 2005 |
| Předmět: |
Receptors
Retinoic Acid Cellular differentiation Retinoic acid Hyperphosphorylation Electrophoretic Mobility Shift Assay HL-60 Cells Tretinoin CD38 Biology Retinoblastoma Protein Focal adhesion chemistry.chemical_compound CCAAT-Enhancer-Binding Protein-alpha Humans Phosphorylation neoplasms Cell Proliferation CD11b Antigen Cell growth Retinoic Acid Receptor alpha Retinoblastoma protein Cell Differentiation Cell Biology Molecular biology ADP-ribosyl Cyclase 1 Cell biology chemistry Apoptosis Focal Adhesion Kinase 1 biology.protein biological phenomena cell phenomena and immunity |
| Zdroj: | Cellular signalling. 18(7) |
| ISSN: | 0898-6568 |
| Popis: | 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 muM 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/EBPalpha was activated in ATRA-treated HL-60/Vect cells but not in HL-60/FAK cells, indicating that c/EBPalpha activation by ATRA was impaired in HL-60/FAK cells. In addition, the association of retinoblastoma protein (pRb) and c/EBPalpha 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/EBPalpha. |
| Databáze: | OpenAIRE |
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