The Mathematical Institute, University of Oxford, Eprints Archive

A mathematical model of the effects of hypoxia on the cell-cycle of normal and cancer cells

Alarcon, T. and Byrne, H. M. and Maini, P. K. (2004) A mathematical model of the effects of hypoxia on the cell-cycle of normal and cancer cells. Journal of theoretical Biology, 229 (3). pp. 395-411.

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Abstract

The evolution of the cell-cycle is known to be influenced by environmental conditions, including lack of extracellular oxygen (hypoxia). Notably, hypoxia appears to have different effects on normal and cancer cells. Whereas both experience hypoxia-induced arrest of the G1 phase of the cell-cycle (i.e. delay in the transition through the restriction point), experimental evidence suggests that only cancer cells undergo hypoxia-induced quiescence (i.e. the transition of the cell to a latent state in which most of the cell functions, including proliferation, are suspended).

Here, we extend a model for the cell-cycle due to Tyson and Novak (J. Theor. Biol. 210 (2001) 249) to account for the action of the protein p27. This protein, whose expression is upregulated under hypoxia, inhibits the activation of the cyclin dependent kinases (CDKs), thus preventing DNA synthesis and delaying the normal progression through the cell-cycle. We use a combination of numerical and analytic techniques to study our model. We show that it reproduces many features of the response to hypoxia of normal and cancer cells, as well as generating experimentally testable predictions. For example our model predicts that cancer cells can undergo quiescence by increasing their levels of p27, whereas for normal cells p27 expression decreases when the cellular growth rate increases.

Item Type:Article
Uncontrolled Keywords:Cell-cycle; Hypoxia; Cancer; p27
Subjects:A - C > Biology and other natural sciences
Research Groups:Centre for Mathematical Biology
ID Code:363
Deposited By:Philip Maini
Deposited On:16 Nov 2006
Last Modified:20 Jul 2009 14:20

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