Induction of HL-60 cells to undergo apoptosis is determined by high levels of wild-type p53 protein whereas differentiation of the cells is mediated by lower p53 levels.
The observation that wild-type p53 may induce cells to undergo either apoptosis or differentiation raises the question of whether these two events share similar p53-dependent pathways. To evaluate the interrelationship between these two p53-dependent processes, our study focused on the human HL-60, a promyelocytic p53 nonproducer cell line in which p53 expression was introduced and the induction of apoptosis and differentiation was followed under controlled conditions. p53 expression was induced in the HL-60 cell line by infection with the recombinant wild-type p53 (p53WT) vaccinia virus. Viral infection gave rise to cells expressing various levels of wild-type p53 protein. High levels of p53 protein induced cells to undergo rapid apoptosis, whereas lower levels of p53 protein induced cells to undergo cell differentiation at a more moderate rate of kinetics. These results suggest that p53 protein levels may determine whether a given cell should prefer one pathway over the other to exit the cell cycle. Accordingly, we propose that the p53 vaccinia virus may be used as a potential vector for cell therapy leading toward the exit of p53 null human primary hematopoetic tumors from the malignant state in vivo via the apoptotic or cell differentiation pathways.
Ronen
D
D
Department of Human Microbiology, Tel Aviv University, Ramat Aviv, Israel.
Schwartz
D
D
Teitz
Y
Y
Goldfinger
N
N
Rotter
V
V
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D018922:HL-60 Cells / Q000166:cytology*; D006801:Humans; D007700:Kinetics; D011994:Recombinant Proteins / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014616:Vaccinia virus / Q000235:genetics
D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53