Cell Growth & Differentiation, Vol 6, Issue 10 1207-1212, Copyright © 1995 by American Association of Cancer Research

ARTICLES

Effects of a recombinant adenovirus expressing WAF1/Cip1 on cell growth, cell cycle, and apoptosis

D Katayose, R Wersto, KH Cowan and P Seth
Medical Breast Cancer Section, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.

To evaluate the effects of a p53-inducible gene WAF1/Cip1 on cell proliferation and apoptosis, a recombinant adenovirus vector (E1 minus) expressing WAF1/Cip1 cDNA (AdWAF1) was constructed and compared with a previously studied recombinant adenovirus vector expressing wild-type p53 (AdWTp53). Infection of normal and tumor cells of lung and mammary epithelial origin with AdWAF1 resulted in high levels of WAF1/Cip1 gene expression, which was comparable to that induced by AdWTp53. AdWAF1 and AdWTp53 inhibited growth of all cells studied; tumor cells devoid of endogenous p53 (H-358) or cells expressing endogenous mutant p53 (MDA-MB-231) were more sensitive to the inhibitory effect than tumor (MCF-7) or normal mammary epithelial cells expressing endogenous wild-type p53. Cell cycle analysis of AdWTp53-infected cells indicated a decline in the cell number in S phase and a significant increase in cell number in G2-M phase. AdWAF1 infection also led to a decline in the percentage of cells in S phase and a significant accumulation of cells in G1. AdWAF1 failed to induce apoptosis in any of the cells tested. In contrast, AdWTp53 induced apoptosis in H-358 and in MDA-MB-231 cells. These data suggest that AdWTp53-mediated WAF1/Cip1 induction and cytotoxicity are likely to be associated with WAF1/Cip1-mediated cell cycle arrest. However, because overexpression of WAF1/Cip1 protein failed to induce apoptosis, AdWTp53 effects on apoptosis apparently require cellular factors in addition to WAF1/Cip1 induction.

This article has been cited by other articles:

				A. K. Khanna, M. Plummer, V. Nilakantan, and G. M. Pieper Recombinant p21 Protein Inhibits Lymphocyte Proliferation and Transcription Factors J. Immunol., June 15, 2005; 174(12): 7610 - 7617. [Abstract] [Full Text] [PDF]

				C. M. Hattinger, A. G. Jochemsen, H. J. Tanke, and R. W. Dirks Induction of p21 mRNA Synthesis After Short-wavelength UV Light Visualized in Individual Cells by RNA FISH J. Histochem. Cytochem., January 1, 2002; 50(1): 81 - 90. [Abstract] [Full Text] [PDF]

				A. Quaroni, J. Q. Tian, P. Seth, and C. Ap Rhys p27Kip1 is an inducer of intestinal epithelial cell differentiation Am J Physiol Cell Physiol, October 1, 2000; 279(4): C1045 - C1057. [Abstract] [Full Text] [PDF]

				A. L. Feldman, N. P. Restifo, H. R. Alexander, D. L. Bartlett, P. Hwu, P. Seth, and S. K. Libutti Antiangiogenic Gene Therapy of Cancer Utilizing a Recombinant Adenovirus to Elevate Systemic Endostatin Levels in Mice Cancer Res., March 1, 2000; 60(6): 1503 - 1506. [Abstract] [Full Text]

				Z. Zou, C. Gao, A. K. Nagaich, T. Connell, S.'i. Saito, J. W. Moul, P. Seth, E. Appella, and S. Srivastava p53 Regulates the Expression of the Tumor Suppressor Gene Maspin J. Biol. Chem., February 25, 2000; 275(9): 6051 - 6054. [Abstract] [Full Text] [PDF]

				G. Lazennec, J. L. Alcorn, and B. S. Katzenellenbogen Adenovirus-Mediated Delivery of a Dominant Negative Estrogen Receptor Gene Abrogates Estrogen-Stimulated Gene Expression and Breast Cancer Cell Proliferation Mol. Endocrinol., June 1, 1999; 13(6): 969 - 980. [Abstract] [Full Text]

				J. L. M. Gervais, P. Seth, and H. Zhang Cleavage of CDK Inhibitor p21Cip1/Waf1 by Caspases Is an Early Event during DNA Damage-induced Apoptosis J. Biol. Chem., July 24, 1998; 273(30): 19207 - 19212. [Abstract] [Full Text] [PDF]

				F. Di Cunto, G. Topley, E. Calautti, J. Hsiao, L. Ong, P. K. Seth, and G. P. Dotto Inhibitory Function of p21Cip1/WAF1 in Differentiation of Primary Mouse Keratinocytes Independent of Cell Cycle Control Science, May 15, 1998; 280(5366): 1069 - 1072. [Abstract] [Full Text]

				B. Harvat, A Wang, P Seth, and A. Jetten Up-regulation of p27Kip1, p21WAF1/Cip1 and p16Ink4a is associated with, but not sufficient for, induction of squamous differentiation J. Cell Sci., January 5, 1998; 111(9): 1185 - 1196. [Abstract] [PDF]

				C. A. Hsu, A. K. Rishi, X. Su-Li, T. M. Gerald, M. I. Dawson, C. Schiffer, U. Reichert, B. Shroot, G. C. Poirer, and J. A. Fontana Retinoid Induced Apoptosis in Leukemia Cells Through a Retinoic Acid Nuclear Receptor-Independent Pathway Blood, June 15, 1997; 89(12): 4470 - 4479. [Abstract] [Full Text] [PDF]