![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 14, No. 1, pp. 34-44, January 1, 2000
1 Johns Hopkins Oncology Center, 2 Department of
Radiology, and 3 Institute of Genetic Medicine, Departments of
Pediatrics and Medicine, The Johns Hopkins University School of
Medicine, Baltimore, Maryland, 21287 USA; 4 Department of
Pediatrics, Stanford University School of Medicine,
Palo Alto, California, 94305 USA
The switch to an angiogenic phenotype is a fundamental determinant
of neoplastic growth and tumor progression. We demonstrate that
homozygous deletion of the p53 tumor suppressor gene via homologous recombination in a human cancer cell line promotes the
neovascularization and growth of tumor xenografts in nude mice. We find
that p53 promotes Mdm2-mediated ubiquitination and proteasomal
degradation of the HIF-1
subunit of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that regulates cellular
energy metabolism and angiogenesis in response to oxygen deprivation.
Loss of p53 in tumor cells enhances HIF-1 levels and
augments HIF-1-dependent transcriptional activation of the vascular
endothelial growth factor (VEGF) gene in response to hypoxia.
Forced expression of HIF-1 in p53-expressing tumor cells increases
hypoxia-induced VEGF expression and augments neovascularization and growth of tumor xenografts. These results indicate that
amplification of normal HIF-1-dependent responses to hypoxia via loss
of p53 function contributes to the angiogenic switch during tumorigenesis.
[Key Words: p53; hypoxia-inducible factor-1 (HIF-1); angiogenesis; vascular endothelial growth factor (VEGF); hypoxia; cancer]
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 S. Weikert, H. Boeing, T. Pischon, C. Weikert, A. Olsen, A. Tjonneland, K. Overvad, N. Becker, J. Linseisen, A. Trichopoulou, et al. Blood Pressure and Risk of Renal Cell Carcinoma in the European Prospective Investigation into Cancer and Nutrition Am. J. Epidemiol., February 15, 2008; 167(4): 438 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Carroll and M. Ashcroft Regulation of Angiogenic Factors by HDM2 in Renal Cell Carcinoma Cancer Res., January 15, 2008; 68(2): 545 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Y. Koh, T. Spivak-Kroizman, S. Venturini, S. Welsh, R. R. Williams, D. L. Kirkpatrick, and G. Powis Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1{alpha} Mol. Cancer Ther., January 1, 2008; 7(1): 90 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. L. Semenza Hypoxia-inducible Factor 1 and Human Cancer ASCO Educational Book, January 1, 2008; 2008(1): 548 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tzouvelekis, V. Harokopos, T. Paparountas, N. Oikonomou, A. Chatziioannou, G. Vilaras, E. Tsiambas, A. Karameris, D. Bouros, and V. Aidinis Comparative Expression Profiling in Pulmonary Fibrosis Suggests a Role of Hypoxia-inducible Factor-1{alpha} in Disease Pathogenesis Am. J. Respir. Crit. Care Med., December 1, 2007; 176(11): 1108 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Cai, M. Murakami, H. Si, and E. S. Robertson A Potential {alpha}-Helix Motif in the Amino Terminus of LANA Encoded by Kaposi's Sarcoma-Associated Herpesvirus Is Critical for Nuclear Accumulation of HIF-1{alpha} in Normoxia J. Virol., October 1, 2007; 81(19): 10413 - 10423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Albini, D. M. Noonan, and N. Ferrari Molecular Pathways for Cancer Angioprevention Clin. Cancer Res., August 1, 2007; 13(15): 4320 - 4325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Rempe, K. M. Lelli, G. Vangeison, R. S. Johnson, and H. J. Federoff In Cultured Astrocytes, p53 and MDM2 Do Not Alter Hypoxia-inducible Factor-1{alpha} Function Regardless of the Presence of DNA Damage J. Biol. Chem., June 1, 2007; 282(22): 16187 - 16201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Menendez, A. Inga, J. Snipe, O. Krysiak, G. Schonfelder, and M. A. Resnick A Single-Nucleotide Polymorphism in a Half-Binding Site Creates p53 and Estrogen Receptor Control of Vascular Endothelial Growth Factor Receptor 1 Mol. Cell. Biol., April 1, 2007; 27(7): 2590 - 2600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-J. Kim, H. Chung, Y.-G. Yoo, H. Kim, J.-Y. Lee, M.-O. Lee, and G. Kong Inhibitor of DNA Binding 1 Activates Vascular Endothelial Growth Factor through Enhancing the Stability and Activity of Hypoxia-Inducible Factor-1{alpha} Mol. Cancer Res., April 1, 2007; 5(4): 321 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Fang, Q. Zhou, L.-Z. Liu, C. Xia, X. Hu, X. Shi, and B.-H. Jiang Apigenin inhibits tumor angiogenesis through decreasing HIF-1{alpha} and VEGF expression Carcinogenesis, April 1, 2007; 28(4): 858 - 864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Lim, J.-W. Park, S. J. Kim, M.-S. Kim, S.-K. Park, R. S. Johnson, and Y.-S. Chun ATP6V0C Competes with Von Hippel-Lindau Protein in Hypoxia-Inducible Factor 1{alpha} (HIF-1{alpha}) Binding and Mediates HIF-1{alpha} Expression by Bafilomycin A1 Mol. Pharmacol., March 1, 2007; 71(3): 942 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Birle and D. W. Hedley Suppression of the Hypoxia-Inducible Factor-1 Response in Cervical Carcinoma Xenografts by Proteasome Inhibitors Cancer Res., February 15, 2007; 67(4): 1735 - 1743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. LaRusch, M. W. Jackson, J. D. Dunbar, R. S. Warren, D. B. Donner, and L. D. Mayo Nutlin3 Blocks Vascular Endothelial Growth Factor Induction by Preventing the Interaction between Hypoxia Inducible Factor 1{alpha} and Hdm2 Cancer Res., January 15, 2007; 67(2): 450 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Evans, R. C. Russell, O. Roche, T. N. Burry, J. E. Fish, V. W. K. Chow, W. Y. Kim, A. Saravanan, M. A. Maynard, M. L. Gervais, et al. VHL Promotes E2 Box-Dependent E-Cadherin Transcription by HIF-Mediated Regulation of SIP1 and Snail Mol. Cell. Biol., January 1, 2007; 27(1): 157 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tanaka, M. Yamamoto, N. Hashimoto, M. Miyakoshi, S. Tamakawa, M. Yoshie, Y. Tokusashi, K. Yokoyama, Y. Yaginuma, and K. Ogawa Hypoxia-Independent Overexpression of Hypoxia-Inducible Factor 1{alpha} as an Early Change in Mouse Hepatocarcinogenesis Cancer Res., December 1, 2006; 66(23): 11263 - 11270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Patiar and A. L Harris Role of hypoxia-inducible factor-1{alpha} as a cancer therapy target Endocr. Relat. Cancer, December 1, 2006; 13(Supplement_1): S61 - S75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Ke and M. Costa Hypoxia-Inducible Factor-1 (HIF-1) Mol. Pharmacol., November 1, 2006; 70(5): 1469 - 1480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Folkman Tumor Suppression by p53 Is Mediated in Part by the Antiangiogenic Activity of Endostatin and Tumstatin Sci. Signal., September 26, 2006; 2006(354): pe35 - pe35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Serganova, J. Humm, C. Ling, and R. Blasberg Tumor hypoxia imaging. Clin. Cancer Res., September 15, 2006; 12(18): 5260 - 5264. [Full Text] [PDF]
|
|
|
|
|
|
D. T. Jones, C. W. Pugh, S. Wigfield, M. F.G. Stevens, and A. L. Harris Novel Thioredoxin Inhibitors Paradoxically Increase Hypoxia-Inducible Factor-{alpha} Expression but Decrease Functional Transcriptional Activity, DNA Binding, and Degradation. Clin. Cancer Res., September 15, 2006; 12(18): 5384 - 5394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. Jones and A. L. Harris Identification of novel small-molecule inhibitors of hypoxia-inducible factor-1 transactivation and DNA binding. Mol. Cancer Ther., September 1, 2006; 5(9): 2193 - 2202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Hammond and A. J. Giaccia Hypoxia-Inducible Factor-1 and p53: Friends, Acquaintances, or Strangers? Clin. Cancer Res., September 1, 2006; 12(17): 5007 - 5009. [Full Text] [PDF]
|
|
|
|
|
|
Y. Sumiyoshi, Y. Kakeji, A. Egashira, K. Mizokami, H. Orita, and Y. Maehara Overexpression of Hypoxia-Inducible Factor 1{alpha} and p53 Is a Marker for an Unfavorable Prognosis in Gastric Cancer Clin. Cancer Res., September 1, 2006; 12(17): 5112 - 5117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. McMahon, M. Charbonneau, S. Grandmont, D. E. Richard, and C. M. Dubois Transforming Growth Factor beta1 Induces Hypoxia-inducible Factor-1 Stabilization through Selective Inhibition of PHD2 Expression J. Biol. Chem., August 25, 2006; 281(34): 24171 - 24181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Teodoro, A. E. Parker, X. Zhu, and M. R. Green p53-mediated inhibition of angiogenesis through up-regulation of a collagen prolyl hydroxylase. Science, August 18, 2006; 313(5789): 968 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hubert, S. Paris, J.-P. Piret, N. Ninane, M. Raes, and C. Michiels Casein kinase 2 inhibition decreases hypoxia-inducible factor-1 activity under hypoxia through elevated p53 protein level J. Cell Sci., August 15, 2006; 119(16): 3351 - 3362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. H. Haase Hypoxia-inducible factors in the kidney Am J Physiol Renal Physiol, August 1, 2006; 291(2): F271 - F281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Qin, R. Kishore, C. M. Dolan, M. Silver, A. Wecker, C. N. Luedemann, T. Thorne, A. Hanley, C. Curry, L. Heyd, et al. Cell cycle regulator E2F1 modulates angiogenesis via p53-dependent transcriptional control of VEGF PNAS, July 18, 2006; 103(29): 11015 - 11020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Zhang, S.-Y. Wang, A. C. Nottke, J. V. Rocheleau, D. W. Piston, and R. H. Goodman Redox sensor CtBP mediates hypoxia-induced tumor cell migration PNAS, June 13, 2006; 103(24): 9029 - 9033. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Enatsu, A. Iwasaki, T. Shirakusa, M. Hamasaki, K. Nabeshima, H. Iwasaki, M. Kuroki, and M. Kuroki Expression of hypoxia-inducible factor-1 alpha and its prognostic significance in small-sized adenocarcinomas of the lung. Eur. J. Cardiothorac. Surg., June 1, 2006; 29(6): 891 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Fath, X. Kong, D. Liang, Z. Lin, A. Chou, Y. Jiang, J. Fang, J. Caro, and N. Sang Histone Deacetylase Inhibitors Repress the Transactivation Potential of Hypoxia-inducible Factors Independently of Direct Acetylation of HIF-{alpha} J. Biol. Chem., May 12, 2006; 281(19): 13612 - 13619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Kong, Z. Lin, D. Liang, D. Fath, N. Sang, and J. Caro Histone Deacetylase Inhibitors Induce VHL and Ubiquitin-Independent Proteasomal Degradation of Hypoxia-Inducible Factor 1{alpha}. Mol. Cell. Biol., March 1, 2006; 26(6): 2019 - 2028. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. Dang, F. Chen, L. B. Gardner, J. M. Cummins, C. Rago, F. Bunz, S. V. Kantsevoy, and L. H. Dang Hypoxia-Inducible Factor-1{alpha} Promotes Nonhypoxia-Mediated Proliferation in Colon Cancer Cells and Xenografts Cancer Res., February 1, 2006; 66(3): 1684 - 1693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Y. Yeung, K. P. Lai, H. Y. Chan, N. K. Mak, G. F. Wagner, and C. K. C. Wong Hypoxia-Inducible Factor-1-Mediated Activation of Stanniocalcin-1 in Human Cancer Cells Endocrinology, November 1, 2005; 146(11): 4951 - 4960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Cristi, G Perrone, G Toscano, A Verzi, S Nori, D Santini, G Tonini, A Vetrani, A Fabiano, and C Rabitti Tumour proliferation, angiogenesis, and ploidy status in human colon cancer J. Clin. Pathol., November 1, 2005; 58(11): 1170 - 1174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Wenger, D. P. Stiehl, and G. Camenisch Integration of Oxygen Signaling at the Consensus HRE Sci. Signal., October 18, 2005; 2005(306): re12 - re12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. Dang, F. Chen, M. Kohli, C. Rago, J. M. Cummins, and L. H. Dang Glutathione S-Transferase {pi}1 Promotes Tumorigenicity in HCT116 Human Colon Cancer Cells Cancer Res., October 15, 2005; 65(20): 9485 - 9494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kong, E. J. Park, A. G. Stephen, M. Calvani, J. H. Cardellina, A. Monks, R. J. Fisher, R. H. Shoemaker, and G. Melillo Echinomycin, a Small-Molecule Inhibitor of Hypoxia-Inducible Factor-1 DNA-Binding Activity Cancer Res., October 1, 2005; 65(19): 9047 - 9055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Maynard, A. J. Evans, T. Hosomi, S. Hara, M. A. S. Jewett, and M. Ohh Human HIF-3{alpha}4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma FASEB J, September 1, 2005; 19(11): 1396 - 1406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Trisciuoglio, A. Iervolino, G. Zupi, and D. Del Bufalo Involvement of PI3K and MAPK Signaling in bcl-2-induced Vascular Endothelial Growth Factor Expression in Melanoma Cells Mol. Biol. Cell, September 1, 2005; 16(9): 4153 - 4162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. W. Newcomb, M. A. Ali, T. Schnee, L. Lan, Y. Lukyanov, M. Fowkes, D. C. Miller, and D. Zagzag Flavopiridol downregulates hypoxia-mediated hypoxia-inducible factor-1{alpha} expression in human glioma cells by a proteasome-independent pathway: Implications for in vivo therapy Neuro-oncol, July 1, 2005; 7(3): 225 - 235. [Abstract] [PDF]
|
|
|
|
|
|
R. R. Raval, K. W. Lau, M. G. B. Tran, H. M. Sowter, S. J. Mandriota, J.-L. Li, C. W. Pugh, P. H. Maxwell, A. L. Harris, and P. J. Ratcliffe Contrasting Properties of Hypoxia-Inducible Factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-Associated Renal Cell Carcinoma Mol. Cell. Biol., July 1, 2005; 25(13): 5675 - 5686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Cao, C.-Y. Li, B. J. Moeller, D. Yu, Y. Zhao, M. R. Dreher, S. Shan, and M. W. Dewhirst Observation of Incipient Tumor Angiogenesis That Is Independent of Hypoxia and Hypoxia Inducible Factor-1 Activation Cancer Res., July 1, 2005; 65(13): 5498 - 5505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-D. CHEN, C.-J. HU, D.-I YANG, A. NASSIEF, H. CHEN, K. YIN, J. XU, and C. Y. HSU Pravastatin Attenuates Ceramide-Induced Cytotoxicity in Mouse Cerebral Endothelial Cells with HIF-1 Activation and VEGF Upregulation Ann. N.Y. Acad. Sci., May 1, 2005; 1042(1): 357 - 364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Kaur, F. W. Khwaja, E. A. Severson, S. L. Matheny, D. J. Brat, and E. G. Van Meir Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis Neuro-oncol, April 1, 2005; 7(2): 134 - 153. [Abstract] [PDF]
|
|
|
|
 |
|
 W.-T. Chen, C.-J. Huang, M.-T. Wu, S.-F. Yang, Y.-C. Su, and C.-Y. Chai Hypoxia-inducible Factor-1{alpha} is Associated with Risk of Aggressive Behavior and Tumor Angiogenesis in Gastrointestinal Stromal Tumor Jpn. J. Clin. Oncol., April 1, 2005; 35(4): 207 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Pietrowski, H. Bettendorf, E.-K. Riener, C. Keck, L. A. Hefler, J. C. Huber, and C. Tempfer Recurrent pregnancy failure is associated with a polymorphism in the p53 tumour suppressor gene Hum. Reprod., April 1, 2005; 20(4): 848 - 851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nakanishi, S. Hiroi, S. Tominaga, S. Aida, H. Kasamatsu, S. Matsuyama, T. Matsuyama, and T. Kawai Expression of Hypoxia-Inducible Factor-1{alpha} Protein Predicts Survival in Patients with Transitional Cell Carcinoma of the Upper Urinary Tract Clin. Cancer Res., April 1, 2005; 11(7): 2583 - 2590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fang, C. Xia, Z. Cao, J. Z. Zheng, E. Reed, and B.-H. Jiang Apigenin inhibits VEGF and HIF-1 expression via PI3K/AKT/p70S6K1 and HDM2/p53 pathways FASEB J, March 1, 2005; 19(3): 342 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-H. Liu, A. Kirschenbaum, K. Yu, S. Yao, and A. C. Levine Cyclooxygenase-2 Suppresses Hypoxia-induced Apoptosis via a Combination of Direct and Indirect Inhibition of p53 Activity in a Human Prostate Cancer Cell Line J. Biol. Chem., February 4, 2005; 280(5): 3817 - 3823. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-G. Yoo, M. G. Yeo, D. K. Kim, H. Park, and M.-O. Lee Novel Function of Orphan Nuclear Receptor Nur77 in Stabilizing Hypoxia-inducible Factor-1{alpha} J. Biol. Chem., December 17, 2004; 279(51): 53365 - 53373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hoeben, B. Landuyt, M. S. Highley, H. Wildiers, A. T. Van Oosterom, and E. A. De Bruijn Vascular Endothelial Growth Factor and Angiogenesis Pharmacol. Rev., December 1, 2004; 56(4): 549 - 580. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Vaupel The Role of Hypoxia-Induced Factors in Tumor Progression Oncologist, November 1, 2004; 9(suppl_5): 10 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A E Greijer and E van der Wall The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis J. Clin. Pathol., October 1, 2004; 57(10): 1009 - 1014. [Abstract] [Full Text] [PDF]
|
|
