Cancer Research AACR Conference on Molecular Diagnostics - 2008 Translational Medicine Conference in Israel
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 Zhang, L.
Right arrow Articles by Hill, R. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, L.
Right arrow Articles by Hill, R. P.
[Cancer Research 64, 4180-4189, June 15, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Hypoxia Enhances Metastatic Efficiency by Up-Regulating Mdm2 in KHT Cells and Increasing Resistance to Apoptosis

Li Zhang1,2 and Richard P. Hill1,2,3

1 Research Division, Ontario Cancer Institute/Princess Margaret Hospital, 2 Department of Medical Biophysics, and 3 Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

Tumor hypoxia has been reported to be a negative prognostic factor in a number of tumor sites. Both clinical and experimental studies have suggested a positive correlation between tumor hypoxia and increased metastatic efficiency; however, the mechanisms are not understood. In this study, the mechanisms of hypoxia-enhanced metastasis have been investigated in murine KHT fibrosarcoma and SCC VII cells. We have observed that hypoxia-pretreated KHT-C cells have a higher survival rate than control KHT-C cells after being arrested in mouse lungs. cDNA microarray analysis revealed many hypoxia-regulated genes, most of which have been reported to be involved in cell survival and growth. Among these genes, we have confirmed the up-regulation of Mdm2 by hypoxia and have demonstrated that this up-regulation is p53 independent. The up-regulation of Mdm2 by hypoxia is associated with decreased p53 protein and inhibition of the transactivation of p53 downstream proapoptotic genes. Overexpression of Mdm2 or suppression of p53 by transient transfection increased metastatic efficiency in KHT-C cells. These data suggest that hypoxia can increase tumor cell metastatic efficiency by rendering the tumor cells less sensitive to stress-induced cell death, e.g., through modifying the levels of Mdm2 and p53.




This article has been cited by other articles:


Home page
 Molecular Cancer TherapeuticsHome page
S. Supiot, R. P. Hill, and R. G. Bristow
Nutlin-3 radiosensitizes hypoxic prostate cancer cells independent of p53
Mol. Cancer Ther., April 1, 2008; 7(4): 993 - 999.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. W. Hebbard, M. Garlatti, L. J.T. Young, R. D. Cardiff, R. G. Oshima, and B. Ranscht
T-cadherin Supports Angiogenesis and Adiponectin Association with the Vasculature in a Mouse Mammary Tumor Model
Cancer Res., March 1, 2008; 68(5): 1407 - 1416.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Zhang and R. P. Hill
Hypoxia Enhances Metastatic Efficiency in HT1080 Fibrosarcoma Cells by Increasing Cell Survival in Lungs, Not Cell Adhesion and Invasion
Cancer Res., August 15, 2007; 67(16): 7789 - 7797.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Zhou, Y. Zhai, Y. Cui, X. Zhang, X. Dong, H. Yang, Y. He, K. Yao, H. Zhang, L. Zhi, et al.
MDM2 Promoter SNP309 Is Associated with Risk of Occurrence and Advanced Lymph Node Metastasis of Nasopharyngeal Carcinoma in Chinese Population
Clin. Cancer Res., May 1, 2007; 13(9): 2627 - 2633.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
N. Chaudary and R. P. Hill
Hypoxia and Metastasis
Clin. Cancer Res., April 1, 2007; 13(7): 1947 - 1949.
[Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J.-Y. Yang, C. S. Zong, W. Xia, Y. Wei, M. Ali-Seyed, Z. Li, K. Broglio, D. A. Berry, and M.-C. Hung
MDM2 Promotes Cell Motility and Invasiveness by Regulating E-Cadherin Degradation.
Mol. Cell. Biol., October 1, 2006; 26(19): 7269 - 7282.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
E. K. Rofstad, B. Mathiesen, K. Kindem, and K. Galappathi
Acidic Extracellular pH Promotes Experimental Metastasis of Human Melanoma Cells in Athymic Nude Mice.
Cancer Res., July 1, 2006; 66(13): 6699 - 6707.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. P. Hill
Identifying Cancer Stem Cells in Solid Tumors: Case Not Proven
Cancer Res., February 15, 2006; 66(4): 1891 - 1896.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. J. Lunt, B. A. Telfer, R. J. Fitzmaurice, I. J. Stratford, and K. J. Williams
Tirapazamine Administered as a Neoadjuvant to Radiotherapy Reduces Metastatic Dissemination
Clin. Cancer Res., June 1, 2005; 11(11): 4212 - 4216.
[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 © 2004 by the American Association for Cancer Research.