CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Athanassiou, M.
Right arrow Articles by Mikheev, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Athanassiou, M.
Right arrow Articles by Mikheev, A. M.
Cell Growth & Differentiation Vol. 10, 729-737, November 1999
© 1999 American Association for Cancer Research


Articles

Stabilization and Reactivation of the p53 Tumor Suppressor Protein in Nontumorigenic Revertants of HeLa Cervical Cancer Cells1

Maria Athanassiou2, Yanwen Hu, Lichen Jing, Benoit Houle3, Helmut Zarbl and Andrei M. Mikheev2,, 4

Program in Cancer Biology, Division of Public Health, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104-2092 [M. A., L. J., B. H., H. Z., A. M. M.], and Division of Toxicology and Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 [M. A., Y. H., B. H., H. Z., A. M. M.]

Abstract

We demonstrated previously that loss of in vitro transformation and in vivo tumorigenicity in two independent revertant clones of HeLa cells (designated HA and HF) resulted from dominant-acting genetic changes. Analysis of the p53 tumor suppressor gene revealed stabilization and at least partial restoration of wild-type p53 transactivation properties pathways in both revertants of HPV-induced cell transformation. The half-lives of the p53 protein and both of the HA and HF clones were increased {approx}4 fold compared with the parental HeLa cells (16, 17, and 4 min, respectively). The levels of E6 viral protein expression were similar in the three cell lines, whereas the levels of the ubiquitin ligase protein, E6 associated protein (E6-AP), were elevated in the revertants. Western blot analysis of immunoaffinity-purified p53 demonstrated that stabilization of p53 in the revertants was correlated with a reduction in the in vivo formation of complexes involving the E6 oncoprotein and p53. Stabilization of p53 function in the revertants did not result from mutations in either the p53 or E6-AP genes. Despite the observed stabilization and restoration of p53 transactivation function in the revertants, exposure of the revertants to DNA-damaging agents did not result in elevated levels of p21waf-1 protein and failed to induce growth arrest in the G1 phase of the cell cycle. However, p53-independent induction of p21waf-1 protein also failed to induce the G1 phase of the cell cycle. Thus, restoration of wild-type p53 transactivation activity in the HA and HF revertants is insufficient to induce G1 arrest and reversion from HPV-induced cell transformation in our model system.




This article has been cited by other articles:


Home page
J. Virol.Home page
R. L. Turner, P. Groitl, T. Dobner, and D. A. Ornelles
Adenovirus Replaces Mitotic Checkpoint Controls
J. Virol., May 1, 2015; 89(9): 5083 - 5096.
[Abstract] [Full Text] [PDF]


Home page
Mol Cancer ResHome page
T. Zhang, P. Wang, H. Ren, J. Fan, and G. Wang
NGFI-B Nuclear Orphan Receptor Nurr1 Interacts with p53 and Suppresses Its Transcriptional Activity
Mol. Cancer Res., August 1, 2009; 7(8): 1408 - 1415.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
O. I. Koues, R. K. Dudley, A. D. Truax, D. Gerhardt, K. P. Bhat, S. McNeal, and S. F. Greer
Regulation of Acetylation at the Major Histocompatibility Complex Class II Proximal Promoter by the 19S Proteasomal ATPase Sug1
Mol. Cell. Biol., October 1, 2008; 28(19): 5837 - 5850.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
N. Ke, G. Claassen, D.-H. Yu, A. Albers, W. Fan, P. Tan, M. Grifman, X. Hu, K. DeFife, V. Nguy, et al.
Nuclear Hormone Receptor NR4A2 Is Involved in Cell Transformation and Apoptosis
Cancer Res., November 15, 2004; 64(22): 8208 - 8212.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
S. Takahashi, S. Saito, N. Ohtani, and T. Sakai
Involvement of the Oct-1 Regulatory Element of the gadd45 Promoter in the p53-independent Response to Ultraviolet Irradiation
Cancer Res., February 1, 2001; 61(3): 1187 - 1195.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
T. Itoshima, T. Fujiwara, T. Waku, J. Shao, M. Kataoka, W. G. Yarbrough, T.-J. Liu, J. A. Roth, N. Tanaka, and M. Kodama
Induction of Apoptosis in Human Esophageal Cancer Cells by Sequential Transfer of the Wild-Type p53 and E2F-1 Genes: Involvement of p53 Accumulation via ARF-mediated MDM2 Down-Regulation
Clin. Cancer Res., July 1, 2000; 6(7): 2851 - 2859.
[Abstract] [Full Text]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1999 by the American Association of Cancer Research.