JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Originally published In Press as doi:10.1074/jbc.M411890200 on February 7, 2005

J. Biol. Chem., Vol. 280, Issue 14, 14349-14355, April 8, 2005
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
280/14/14349    most recent
M411890200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 Flatten, K.
Right arrow Articles by Kaufmann, S. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Flatten, K.
Right arrow Articles by Kaufmann, S. H.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

The Role of Checkpoint Kinase 1 in Sensitivity to Topoisomerase I Poisons*

Karen Flatten{ddagger}, Nga T. Dai{ddagger}, Benjamin T. Vroman{ddagger}, David Loegering{ddagger}, Charles Erlichman§, Larry M. Karnitz{ddagger}||**, and Scott H. Kaufmann{ddagger}||{ddagger}{ddagger}

From the Divisions of {ddagger}Oncology Research and §Medical Oncology, Mayo Clinic and Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota 55905

Agents that target topoisomerase I are widely utilized to treat human cancer. Previous studies have indicated that both the ataxia telangiectasia mutated (ATM)/checkpoint kinase (Chk) 2 and ATM- and Rad 3-related (ATR)/Chk1 checkpoint pathways are activated after treatment with these agents. The relative contributions of these two pathways to survival of cells after treatment with topoisomerase I poisons are currently unknown. To address this issue, we assessed the roles of ATR, Chk1, ATM, and Chk2 in cells treated with the topoisomerase I poisons camptothecin and 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan. Colony forming assays demonstrated that down-regulation of ATR or Chk1 sensitized cells to SN-38 and camptothecin. In contrast, ATM and Chk2 had minimal effect of sensitivity to SN-38 or camptothecin. Additional experiments demonstrated that the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin, which down-regulates Chk1, also sensitized a variety of human carcinoma cell lines to SN-38. Collectively, these results show that the ATR/Chk1 pathway plays a predominant role in the response to topoisomerase I inhibitors in carcinoma cells and identify a potential approach for enhancing the efficacy of these drugs.


Received for publication, October 19, 2004 , and in revised form, January 4, 2005.

* This work was supported in part by National Institutes of Health Grants CA73709 (to S. H. K.), CA104378 (to L. M. K.), and CA90390 (to C. E.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

|| Both authors contributed equally to this work.

** To whom correspondence may be addressed: Div. of Oncology Research, Guggenheim 1301, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905. Phone: 507-284-3124; Fax: 507-284-3906; E-mail: Karnitz.Larry{at}Mayo.edu. {ddagger}{ddagger} To whom may be addressed: Div. of Oncology Research, Guggenheim 1301, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905. Tel.: 507-284-8950; Fax: 507-284-3906; E-mail: Kaufmann.Scott{at}Mayo.edu.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
MutagenesisHome page
L. C. Riches, A. M. Lynch, and N. J. Gooderham
Early Events in the Mammalian Response to DNA Double-Strand Breaks
Mutagenesis, July 21, 2008; (2008) gen039v1.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
M. Huang, Z.-H. Miao, H. Zhu, Y.-J. Cai, W. Lu, and J. Ding
Chk1 and Chk2 are differentially involved in homologous recombination repair and cell cycle arrest in response to DNA double-strand breaks induced by camptothecins
Mol. Cancer Ther., June 1, 2008; 7(6): 1440 - 1449.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
S. Ray, S. Shyam, G. C. Fraizer, and A. Almasan
S-phase checkpoints regulate Apo2 ligand/TRAIL and CPT-11-induced apoptosis of prostate cancer cells
Mol. Cancer Ther., April 1, 2007; 6(4): 1368 - 1378.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
D. Wilsker and F. Bunz
Loss of ataxia telangiectasia mutated- and Rad3-related function potentiates the effects of chemotherapeutic drugs on cancer cell survival
Mol. Cancer Ther., April 1, 2007; 6(4): 1406 - 1413.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
A. N. Tse, R. Carvajal, and G. K. Schwartz
Targeting Checkpoint Kinase 1 in Cancer Therapeutics
Clin. Cancer Res., April 1, 2007; 13(7): 1955 - 1960.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
A. I. Robles, M. H. Wright, B. Gandhi, S. S. Feis, C. L. Hanigan, A. Wiestner, and L. Varticovski
Schedule-Dependent Synergy between the Heat Shock Protein 90 Inhibitor 17-(Dimethylaminoethylamino)-17-Demethoxygeldanamycin and Doxorubicin Restores Apoptosis to p53-Mutant Lymphoma Cell Lines.
Clin. Cancer Res., November 1, 2006; 12(21): 6547 - 6556.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
H. Takemura, V. A. Rao, O. Sordet, T. Furuta, Z.-H. Miao, L. Meng, H. Zhang, and Y. Pommier
Defective Mre11-dependent Activation of Chk2 by Ataxia Telangiectasia Mutated in Colorectal Carcinoma Cells in Response to Replication-dependent DNA Double Strand Breaks
J. Biol. Chem., October 13, 2006; 281(41): 30814 - 30823.
[Abstract] [Full Text] [PDF]


Home page
Eukaryot CellHome page
I. Malavazi, M. Savoldi, S. M. Z. Di Mauro, C. F. M. Menck, S. D. Harris, M. H. d. S. Goldman, and G. H. Goldman
Transcriptome Analysis of Aspergillus nidulans Exposed to Camptothecin-Induced DNA Damage.
Eukaryot. Cell, October 1, 2006; 5(10): 1688 - 1704.
[Abstract] [Full Text] [PDF]


Home page
Nucleic Acids ResHome page
C. R. Barker, A. V. McNamara, S. A. Rackstraw, D. E. Nelson, M. R. White, A. J. M. Watson, and J. R. Jenkins
Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage
Nucleic Acids Res., February 16, 2006; 34(4): 1148 - 1157.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
C. J. Strock, J.-I. Park, D. M. Rosen, B. Ruggeri, S. R. Denmeade, D. W. Ball, and B. D. Nelkin
Activity of Irinotecan and the Tyrosine Kinase Inhibitor CEP-751 in Medullary Thyroid Cancer
J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 79 - 84.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
S. H. Kaufmann, J. E. Karp, L. Letendre, T. J. Kottke, S. Safgren, J. Greer, I. Gojo, P. Atherton, P. A. Svingen, D. A. Loegering, et al.
Phase I and Pharmacologic Study of Infusional Topotecan and Carboplatin in Relapsed and Refractory Acute Leukemia
Clin. Cancer Res., September 15, 2005; 11(18): 6641 - 6649.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
R. A. Mesa, D. Loegering, H. L. Powell, K. Flatten, S. J. H. Arlander, N. T. Dai, M. P. Heldebrant, B. T. Vroman, B. D. Smith, J. E. Karp, et al.
Heat shock protein 90 inhibition sensitizes acute myelogenous leukemia cells to cytarabine
Blood, July 1, 2005; 106(1): 318 - 327.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.