Open AccessInhibition by Differentiation‐inducing Agents of Wild‐type p53‐dependent Apoptosis in HL‐60 Cells
Author(s) -
Noguchi Kohji,
Nakajima Motowo,
Naito Mikihiko,
Tsuruo Takashi
Publication year - 1995
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1995.tb03042.x
Subject(s) - apoptosis , biology , retinoic acid , programmed cell death , tumor suppressor gene , microbiology and biotechnology , transfection , cellular differentiation , cell cycle , inhibitor of apoptosis domain , kinase , cell culture , cancer research , caspase , gene , biochemistry , carcinogenesis , genetics
The product of the p53 tumor‐suppressor gene has been shown to function in apoptosis and cell cycle regulation. However, there is little information regarding the regulation of apoptosis in cell differentiation. We investigated the relationship between p53‐dependent apoptosis and differentiation induction using human promyelocytic leukemia HL‐60 cells transfected with pMAMneo expression vectors containing dexamethasone‐inducible wild‐type p53 (wt‐p53) cDNA inserts. Continuous exposure of the pMAMneo/wt‐p53 transfectants to 1 μ M , dexamethasone for more than 24 h caused overexpression of wt‐p53 followed by cell death with morphological changes typical of apoptosis. Using the wt‐p53‐inducible HL‐60 cells, we examined the effects of differentiation inducers on the wt‐p53‐dependent apoptosis. All‐ trans retinoic acid (all‐ trans RA) at 1 n M or granulocyte macrophage colonystimulating factor (GM‐CSF) at 35 p M inhibited the wt‐p53‐induced apoptosis over a 42‐h treatment. The apoptosis inhibition by GM‐CSF, but not all trans RA, was abolished by specific inhibitors of protein kinase C. These results suggest that extracellular signals involved in the differentiation induction could modulate the wt‐p53‐dependent apoptosis through protein kinase C‐dependent and independent pathways.