Cancer Research Prevention Award Frontiers in Basic Cancer Research
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
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 reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hirose, Y.
Right arrow Articles by Pieper, R. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hirose, Y.
Right arrow Articles by Pieper, R. O.
[Cancer Research 61, 1957-1963, March 1, 2001]
© 2001 American Association for Cancer Research

Experimental Therapeutics

p53 Effects Both the Duration of G2/M Arrest and the Fate of Temozolomide-treated Human Glioblastoma Cells1

Yuichi Hirose, Mitchel S. Berger and Russell O. Pieper2

Brain Tumor Research Center, Department of Neurological Surgery, and the University of California San Francisco Cancer Center, University of California San Francisco, San Francisco, California 94143-0875

Temozolomide (TMZ) is a DNA-methylating agent that has recently been introduced into Phase II and III trials for the treatment of gliomas. TMZ produces O6-methylguanine in DNA, which mispairs with thymine during the next cycle of DNA replication. Subsequent futile cycles of DNA mismatch repair can lead to a p53-associated apoptotic cell death, although this mechanism has been described mostly in hematopoietic neoplasms. We studied the action of TMZ in gliomas and the role p53 might play by using U87 glioma cells that were either p53-wild-type or p53-deficient (by virtue of expression of the viral oncoprotein E6). LN-Z308 cells, in which p53 gene is deleted, were also used. p53-proficient U87 MG cells underwent a prolonged, p53- and p21Waf1/Cip1-associated G2-M arrest beginning 2 days after TMZ treatment. Although very few of these cells underwent apoptosis, most underwent senescence over a 10-day period. p53-deficient (E6-transfected U87 and LN-Z308) cells similarly underwent G2-M arrest in response to TMZ, but this arrest was accompanied by only minor changes in p53 or p21Waf1/Cip1 and was reversed within 7 days of TMZ treatment in association with the appearance of cells with either 8n or subG1 DNA content. These results suggest that glioma cells respond to TMZ by undergoing G2-M arrest. p53 is not necessary for this G2-M arrest to occur but is important in the duration of G2-M arrest and in the ultimate fate of TMZ-treated cells. Therefore, the integrity of the G2-M cell cycle checkpoint may be important in the cytotoxicity of TMZ in glioma cells.




This article has been cited by other articles:


Home page
 Molecular Cancer TherapeuticsHome page
V. Milano, Y. Piao, T. LaFortune, and J. de Groot
Dasatinib-induced autophagy is enhanced in combination with temozolomide in glioma
Mol. Cancer Ther., February 1, 2009; 8(2): 394 - 406.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Beier, S. Rohrl, D. R. Pillai, S. Schwarz, L. A. Kunz-Schughart, P. Leukel, M. Proescholdt, A. Brawanski, U. Bogdahn, A. Trampe-Kieslich, et al.
Temozolomide Preferentially Depletes Cancer Stem Cells in Glioblastoma
Cancer Res., July 15, 2008; 68(14): 5706 - 5715.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. Stupp, M. E. Hegi, M. R. Gilbert, and A. Chakravarti
Chemoradiotherapy in Malignant Glioma: Standard of Care and Future Directions
J. Clin. Oncol., September 10, 2007; 25(26): 4127 - 4136.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B. Yamini, X. Yu, M. E. Dolan, M. H. Wu, D. W. Kufe, and R. R. Weichselbaum
Inhibition of Nuclear Factor-{kappa}B Activity by Temozolomide Involves O6-Methylguanine Induced Inhibition of p65 DNA Binding
Cancer Res., July 15, 2007; 67(14): 6889 - 6898.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
O. K. Mirzoeva, T. Kawaguchi, and R. O. Pieper
The Mre11/Rad50/Nbs1 complex interacts with the mismatch repair system and contributes to temozolomide-induced G2 arrest and cytotoxicity.
Mol. Cancer Ther., November 1, 2006; 5(11): 2757 - 2766.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Hirose, M. Katayama, O. K. Mirzoeva, M. S. Berger, and R. O. Pieper
Akt Activation Suppresses Chk2-Mediated, Methylating Agent-Induced G2 Arrest and Protects from Temozolomide-Induced Mitotic Catastrophe and Cellular Senescence
Cancer Res., June 1, 2005; 65(11): 4861 - 4869.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B. Yamini, X. Yu, G. Y. Gillespie, D. W. Kufe, and R. R. Weichselbaum
Transcriptional Targeting of Adenovirally Delivered Tumor Necrosis Factor {alpha} by Temozolomide in Experimental Glioblastoma
Cancer Res., September 15, 2004; 64(18): 6381 - 6384.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Gupta, R. A. Schoer, J. E. Egan, G. J. Hannon, and V. Mittal
From the Cover: Inducible, reversible, and stable RNA interference in mammalian cells
PNAS, February 17, 2004; 101(7): 1927 - 1932.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Hirose, M. Katayama, D. Stokoe, D. A. Haas-Kogan, M. S. Berger, and R. O. Pieper
The p38 Mitogen-Activated Protein Kinase Pathway Links the DNA Mismatch Repair System to the G2 Checkpoint and to Resistance to Chemotherapeutic DNA-Methylating Agents
Mol. Cell. Biol., November 15, 2003; 23(22): 8306 - 8315.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. Tentori, C. Leonetti, M. Scarsella, G. d'Amati, M. Vergati, I. Portarena, W. Xu, V. Kalish, G. Zupi, J. Zhang, et al.
Systemic Administration of GPI 15427, a Novel Poly(ADP-Ribose) Polymerase-1 Inhibitor, Increases the Antitumor Activity of Temozolomide against Intracranial Melanoma, Glioma, Lymphoma
Clin. Cancer Res., November 1, 2003; 9(14): 5370 - 5379.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
L. Tentori, I. Portarena, M. Barbarino, A. Balduzzi, L. Levati, M. Vergati, A. Biroccio, B. Gold, M. L. Lombardi, and G. Graziani
Inhibition of Telomerase Increases Resistance of Melanoma Cells to Temozolomide, but Not to Temozolomide Combined with Poly (ADP-Ribose) Polymerase Inhibitor
Mol. Pharmacol., January 1, 2003; 63(1): 192 - 202.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. Stupp, P.-Y. Dietrich, S. O. Kraljevic, A. Pica, I. Maillard, P. Maeder, R. Meuli, R. Janzer, G. Pizzolato, R. Miralbell, et al.
Promising Survival for Patients With Newly Diagnosed Glioblastoma Multiforme Treated With Concomitant Radiation Plus Temozolomide Followed by Adjuvant Temozolomide
J. Clin. Oncol., March 1, 2002; 20(5): 1375 - 1382.
[Abstract] [Full Text] [PDF]

Home page
 MutagenesisHome page
M. L. Smith and Y. R. Seo
p53 regulation of DNA excision repair pathways
Mutagenesis, March 1, 2002; 17(2): 149 - 156.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Hirose, M. S. Berger, and R. O. Pieper
Abrogation of the Chk1-mediated G2 Checkpoint Pathway Potentiates Temozolomide-induced Toxicity in a p53-independent Manner in Human Glioblastoma Cells
Cancer Res., August 1, 2001; 61(15): 5843 - 5849.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2001 by the American Association for Cancer Research.