| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
|
|
|
|
|||||||||||||
|
|
|||||||||||||||
REVIEW |
1 Departments of Pathology and Medical Oncology, VU University Medical Centre, Amsterdam, 1081 HV, The Netherlands
2 Departments of Pathology and Medical Oncology, UMCU, Utrecht, 3508 GA, The Netherlands
Correspondence to:
Dr A E Greijer
Departments of Pathology and Medical Oncology, VU University Medical Centre, Amsterdam, 1081 HV, The Netherlands; ae.greijer{at}vumc.nl
ABSTRACT
Apoptosis can be induced in response to hypoxia. The severity of hypoxia determines whether cells become apoptotic or adapt to hypoxia and survive. A hypoxic environment devoid of nutrients prevents the cell undergoing energy dependent apoptosis and cells become necrotic. Apoptosis regulatory proteins are delicately balanced. In solid tumours, hypoxia is a common phenomenon. Cells adapt to this environmental stress, so that after repeated periods of hypoxia, selection for resistance to hypoxia induced apoptosis occurs. These resistant tumours probably have a more aggressive phenotype and may have decreased responsiveness to treatment. The key regulator of this process, hypoxia inducible factor 1 (HIF-1), can initiate apoptosis by inducing high concentrations of proapoptotic proteins, such as BNIP3, and can cause stabilisation of p53. However, during hypoxia, antiapoptotic proteins, such as IAP-2, can be induced, whereas the proapoptotic protein Bax can be downregulated. During hypoxia, an intricate balance exists between factors that induce or counteract apoptosis, or even stimulate proliferation. Understanding the regulation of apoptosis during hypoxia and the mechanisms of resistance to apoptosis might lead to more specific treatments for solid tumours.
Abbreviations: Apaf-1, apoptotic protease activating factor-1; BNIP3, BCL-2/adenovirus E1B 19 kDa interacting protein 3; ES, embryonic stem; HIF-1, hypoxia inducible factor 1; HRE, hypoxia response element; IAP-2, inhibitor of apoptosis protein2; IRES, internal ribosome entry site; Jab1, jun activation domain binding protein 1; JNK, c-Jun NH2 terminal kinase; NF-
B, nuclear factor B; ODD, oxygen dependent degradation; PI3K, phosphoinositide-3 kinase; ROS, reactive oxygen species; SAPK, stress activated protein kinase; VHL, von Hippel Lindau
Keywords: hypoxia; apoptosis; hypoxia inducible factor 1; tumour
This article has been cited by other articles:
|
|
 |
|
  J. Jantsch, D. Chakravortty, N. Turza, A. T. Prechtel, B. Buchholz, R. G. Gerlach, M. Volke, J. Glasner, C. Warnecke, M. S. Wiesener, et al. Hypoxia and Hypoxia-Inducible Factor-1{alpha} Modulate Lipopolysaccharide-Induced Dendritic Cell Activation and Function J. Immunol., April 1, 2008; 180(7): 4697 - 4705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Nishimura, J. Komiyama, Y. Tasaki, T. J. Acosta, and K. Okuda Hypoxia Promotes Luteal Cell Death in Bovine Corpus Luteum Biol Reprod, March 1, 2008; 78(3): 529 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Furuta, S. K. Pai, R. Zhan, S. Bandyopadhyay, M. Watabe, Y.-Y. Mo, S. Hirota, S. Hosobe, T. Tsukada, K. Miura, et al. Fatty Acid Synthase Gene Is Up-regulated by Hypoxia via Activation of Akt and Sterol Regulatory Element Binding Protein-1 Cancer Res., February 15, 2008; 68(4): 1003 - 1011. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Ray, S. Arab, Y. Deng, P. Liu, L. Penn, D. W. Courtman, and M. E. Ward Oxygen regulation of arterial smooth muscle cell proliferation and survival Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H839 - H852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. May, D. Gilon, V. Djonov, A. Itin, A. Lazarus, O. Gordon, C. Rosenberger, and E. Keshet Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation PNAS, January 8, 2008; 105(1): 282 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. P. Witz Yin-Yang Activities and Vicious Cycles in the Tumor Microenvironment Cancer Res., January 1, 2008; 68(1): 9 - 13. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Klatte, D. B. Seligson, S. B. Riggs, J. T. Leppert, M. K. Berkman, M. D. Kleid, H. Yu, F. F. Kabbinavar, A. J. Pantuck, and A. S. Belldegrun Hypoxia-Inducible Factor 1{alpha} in Clear Cell Renal Cell Carcinoma Clin. Cancer Res., December 15, 2007; 13(24): 7388 - 7393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. O'Brien, V. Barnes, L. Zhao, R. A. McKnight, X. Yu, C. W. Callaway, L. Wang, J. C. Sun, M. J. Dahl, A. Wint, et al. Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR rat lungs Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R314 - R322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. R. Rezvani, S. Dedieu, S. North, F. Belloc, R. Rossignol, T. Letellier, H. de Verneuil, A. Taieb, and F. Mazurier Hypoxia-inducible Factor-1{alpha}, a Key Factor in the Keratinocyte Response to UVB Exposure J. Biol. Chem., June 1, 2007; 282(22): 16413 - 16422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Wouters, B. Pauwels, F. Lardon, and J. B. Vermorken Review: Implications of In Vitro Research on the Effect of Radiotherapy and Chemotherapy Under Hypoxic Conditions Oncologist, June 1, 2007; 12(6): 690 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Cui, S. Darmanin, M. Natsuisaka, T. Kondo, M. Asaka, M. Shindoh, F. Higashino, J. Hamuro, F. Okada, M. Kobayashi, et al. Enhanced Expression of Asparagine Synthetase under Glucose-Deprived Conditions Protects Pancreatic Cancer Cells from Apoptosis Induced by Glucose Deprivation and Cisplatin Cancer Res., April 1, 2007; 67(7): 3345 - 3355. [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]
|
|
|
|
|
|
C. Leo, L.-C. Horn, C. Rauscher, B. Hentschel, C. E. Richter, A. Schutz, C. P. Leo, and M. Hockel Lack of Apoptotic Protease Activating Factor-1 Expression and Resistance to Hypoxia-Induced Apoptosis in Cervical Cancer Clin. Cancer Res., February 15, 2007; 13(4): 1149 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Maher, M. Wangpaichitr, N. Savaraj, M. Kurtoglu, and T. J. Lampidis Hypoxia-inducible factor-1 confers resistance to the glycolytic inhibitor 2-deoxy-D-glucose Mol. Cancer Ther., February 1, 2007; 6(2): 732 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kroemer, L. Galluzzi, and C. Brenner Mitochondrial Membrane Permeabilization in Cell Death Physiol Rev, January 1, 2007; 87(1): 99 - 163. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 R. D. Ward, B. M. Stone, L. T. Raetzman, and S. A. Camper Cell Proliferation and Vascularization in Mouse Models of Pituitary Hormone Deficiency Mol. Endocrinol., June 1, 2006; 20(6): 1378 - 1390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Biju, Y. Akai, N. Shrimanker, and V. H. Haase Protection of HIF-1-deficient primary renal tubular epithelial cells from hypoxia-induced cell death is glucose dependent Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1217 - F1226. [Abstract] [Full Text] [PDF]
|
|
Read all eLetters
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
| Journal of Clinical Pathology | Molecular Pathology |
