Cell Growth & Differentiation, Vol 7, Issue 1 21-30, Copyright © 1996 by American Association of Cancer Research

ARTICLES

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

D Ronen, D Schwartz, Y Teitz, N Goldfinger and V Rotter
Department of Human Microbiology, Tel Aviv University, Ramat Aviv, Israel.

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.

This article has been cited by other articles:

				H. Hosako, S. A. Little, M. Barrier, and P. E. Mirkes Teratogen-Induced Activation of p53 in Early Postimplantation Mouse Embryos Toxicol. Sci., January 1, 2007; 95(1): 257 - 269. [Abstract] [Full Text] [PDF]

				K. L. Harms and X. Chen The C Terminus of p53 Family Proteins Is a Cell Fate Determinant Mol. Cell. Biol., March 1, 2005; 25(5): 2014 - 2030. [Abstract] [Full Text] [PDF]

				A. Inga, F. Storici, T. A. Darden, and M. A. Resnick Differential Transactivation by the p53 Transcription Factor Is Highly Dependent on p53 Level and Promoter Target Sequence Mol. Cell. Biol., December 15, 2002; 22(24): 8612 - 8625. [Abstract] [Full Text] [PDF]

				Z. Humlova, M. Vokurka, M. Esteban, and Z. Melkova Vaccinia virus induces apoptosis of infected macrophages J. Gen. Virol., November 1, 2002; 83(11): 2821 - 2832. [Abstract] [Full Text] [PDF]

				H. Offer, N. Erez, I. Zurer, X. Tang, M. Milyavsky, N. Goldfinger, and V. Rotter The onset of p53-dependent DNA repair or apoptosis is determined by the level of accumulated damaged DNA Carcinogenesis, June 1, 2002; 23(6): 1025 - 1032. [Abstract] [Full Text] [PDF]

				Z. Wu, J. Earle, S.'i. Saito, C. W. Anderson, E. Appella, and Y. Xu Mutation of Mouse p53 Ser23 and the Response to DNA Damage Mol. Cell. Biol., April 15, 2002; 22(8): 2441 - 2449. [Abstract] [Full Text] [PDF]

				A. M. Rodriguez-Lopez, D. Xenaki, T. O. B. Eden, J. A. Hickman, and C. M. Chresta MDM2 Mediated Nuclear Exclusion of p53 Attenuates Etoposide-Induced Apoptosis in Neuroblastoma Cells Mol. Pharmacol., January 1, 2001; 59(1): 135 - 143. [Abstract] [Full Text]

				K. Chylicki, M. Ehinger, H. Svedberg, and U. Gullberg Characterization of the Molecular Mechanisms for p53-mediated Differentiation Cell Growth Differ., November 1, 2000; 11(11): 561 - 571. [Abstract] [Full Text]

				K. Chylicki, M. Ehinger, H. Svedberg, G. Bergh, I. Olsson, and U. Gullberg p53-mediated Differentiation of the Erythroleukemia Cell Line K562 Cell Growth Differ., June 1, 2000; 11(6): 315 - 324. [Abstract] [Full Text]

				G. Schumacher, M. Kataoka, J. A. Roth, and T. Mukhopadhyay Potent Antitumor Activity of 2-Methoxyestradiol in Human Pancreatic Cancer Cell Lines Clin. Cancer Res., March 1, 1999; 5(3): 493 - 499. [Abstract] [Full Text] [PDF]

				J. W. Wilson, D. M. Pritchard, J. A. Hickman, and C. S. Potten Radiation-Induced p53 and p21WAF-1/CIP1 Expression in the Murine Intestinal Epithelium : Apoptosis and Cell Cycle Arrest Am. J. Pathol., September 1, 1998; 153(3): 899 - 909. [Abstract] [Full Text] [PDF]

				J. Zhu, W. Zhou, J. Jiang, and X. Chen Identification of a Novel p53 Functional Domain That Is Necessary for Mediating Apoptosis J. Biol. Chem., May 22, 1998; 273(21): 13030 - 13036. [Abstract] [Full Text] [PDF]

				R. Lev Bar-Or, R. Maya, L. A. Segel, U. Alon, A. J. Levine, and M. Oren Generation of oscillations by the p53-Mdm2 feedback loop: A theoretical and experimental study PNAS, October 10, 2000; 97(21): 11250 - 11255. [Abstract] [Full Text] [PDF]