Hypoxia and Reoxygenation: a Pressure for Mutant p53 Cell Selection and Tumour Progression

✍ Scribed by Kevin E Thompson; Janice A Royds

• Book ID: 102566513
• Publisher: Springer
• Year: 1999
• Tongue: English
• Weight: 196 KB
• Volume: 61
• Category: Article
• ISSN: 1522-9602
• DOI: 10.1006/bulm.1999.0109

✦ Synopsis

Recent findings indicate that in a hypoxic environment, oncogenically transformed cells with a mutant form of the tumour suppressor gene p53 may have a survival advantage over similar cells with wild-type p53. This is because the extent of hypoxia-induced apoptosis has been observed to diminish with the loss of wildtype p53 function in certain cell lines. Hypoxic conditions, common in most solid tumours, may thus provide a physiological pressure to select for cells with mutations in the p53 gene. A new model incorporating cell-specific parameters is proposed here to quantify the survival advantage of mutant or null p53 cells over their wild-type counterparts at any level of oxygen deprivation. Predictions are in good agreement with previous monolayer culture experiments comparing hypoxic survival of null and wild-type p53 cells. By extending the model we are able to investigate the effects of repeated rounds of hypoxia and reoxygenation on a mixture of wild-type and mutant or null p53 cells and determine how many rounds are required before a subpopulation of mutant or null p53 cells overtakes a given population of wild-type p53 cells.