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British Medical Bulletin 53:522-538 (1997)
© 1997 The British Council
research-article |
p53 and apoptosis
Department of Pathology, University Medical School Edinburgh, UK
Christopher O C Bellamy, Department of Pathology, Edinburgh University Medical School, Teviot Place, Edinburgh EH8 9AG, UK
Abstract
Loss of fuction of the p53 tumour suppressor gene is a frequent and important event in the genesis or progession of many human malignancies. Loss of p53 dependent apoptosis is belived to be critical to carcinogenesis in many of these cases, suggesting the possibility to therapeutically restore this pathway and directly eliminate malignant cells or increase or restore their sensitivity to chemotherapeutic agents.
The regulation of p53-dependent responses is complex and variable between cell types, and whether a cell undergoes apoptosis after activation of p53 is highly sensitive to signal context, including environmental and cell intrinsic influences. This article focuses upon p53-dependent apoptosis, considering current understanding of the biochemical steps involved, the factors determining selection of apoptosis over other p53-dependent responses, the significace of p53-dependent apoptosis for the genesis, progression and drug resistance of human cancers, and finally the prospects for clinical manipulaion of this pathway in cancer therapy.
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