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. 1996 Jan 4;379(6560):88-91.
doi: 10.1038/379088a0.

Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours

T G Graeber  1 , C Osmanian, T Jacks, D E Housman, C J Koch, S W Lowe, A J Giaccia
Affiliations

Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours

T G Graeber et al. Nature. .

Abstract

Apoptosis is a genetically encoded programme of cell death that can be activated under physiological conditions and may be an important safeguard against tumour development. Regions of low oxygen (hypoxia) and necrosis are common features of solid tumours. Here we report that hypoxia induces apoptosis in oncogenically transformed cells and that further genetic alterations, such as loss of the p53 tumour-suppressor gene or overexpression of the apoptosis-inhibitor protein Bcl-2, substantially reduce hypoxia-induced cell death. Hypoxia also selects for cells with defects in apoptosis, because small numbers of transformed cells lacking p53 overtake similar cells expressing wild-type p53 when treated with hypoxia. Furthermore, highly apoptotic regions strongly correlate with hypoxic regions in transplanted tumours expressing wild-type p53, whereas little apoptosis occurs in hypoxic regions of p53-deficient tumours. We propose that hypoxia provides a physiological selective pressure in tumours for the expansion of variants that have lost their apoptotic potential, and in particular for cells acquiring p53 mutations.

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Comment in

  • Life (and death) in a malignant tumour.
    Kinzler KW, Vogelstein B. Kinzler KW, et al. Nature. 1996 Jan 4;379(6560):19-20. doi: 10.1038/379019a0. Nature. 1996. PMID: 8538735 No abstract available.
  • Little difference.
    Wenger RH, Gassmann M. Wenger RH, et al. Nature. 1996 Mar 14;380(6570):100. doi: 10.1038/380100d0. Nature. 1996. PMID: 8600376 No abstract available.

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