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Mol Genet Metab. 2000 Jun;70(2):85-98.

P53 and IGFBP-3: apoptosis and cancer protection.

Author information

1
Division of Pediatric Endocrinology, The University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.

Abstract

p53, perhaps the single most important human tumor suppressor, is commonly mutated in human cancers. Normally genotoxic stress and hypoxia activate p53, which, through DNA-specific transcription activation, transcriptional repression, and protein-protein interactions, triggers cell cycle arrest and apoptosis. One of the genes induced by p53 was identified as that encoding the insulin-like growth factor binding protein (IGFBP)-3. IGFBP-3 was originally defined by the somatomedin hypothesis as the principal carrier of IGF-I in the circulation and the primary regulator of the amount of free IGF-I available to interact with the IGF-1 receptor. However, there is accumulating evidence that IGFBP-3 can also cause apoptosis in an IGF-independent manner. Thus, IGFBP-3 induction by p53 constitutes a new means of cross-talk between the p53 and IGF axes, and suggests that the ultimate function of IGFBP-3 may be to serve a protective role against the potentially carcinogenic effects of growth hormone and IGF-I.

PMID:
10873390
DOI:
10.1006/mgme.2000.3008
[Indexed for MEDLINE]

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