Cell cycle deregulation can occur at different levels in cancer. In human breast cancer it includes overexpression of cyclins D1 and E, down-regulation of cyclin-dependent kinase inhibitors and inactivation of the retinoblastoma and p53 tumor suppressor proteins. Telomerase activity is strongly asso
p53 allele losses, mutations and expression in breast cancer and their relationship to clinico-pathological parameters
β Scribed by A. M. Thompson; T. J. Anderson; A. Condie; J. Prosser; U. Chetty; D. C. Carter; H. J. Evans; C. M. Steel
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- French
- Weight
- 761 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0020-7136
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β¦ Synopsis
The p53 locus on the short arm of chromosome I 7 at I7p 13. I was examined for loss of heterozygosity, mutation, rnRNA and protein expression in 60 primary breast cancers. Allele loss around the p53 locus was detected in 19/45 informative turnours (42%). p53 mutations in the evolutionarily conserved exons 5 to 9 were detected in 17/60 (28%) by amplification mismatch and confirmed by direct DNA sequencing. p53 mRNA expression was detected by Northern blot in 36/59 (61Yo) of turnours, and p53 protein expression using antibody 1801 on frozen-tissue sections in 13/44 of the turnours examined. p53 mutation was significantly associated with oestrogen-receptorpoor turnours (p < 0.01) and hence with poor prognosis, but not with other clinical or pathological parameters. There was no statistical correlation between loss of heterozygosity around the p53 locus at 17p 13. I and p53 mutation. Furthermore, p53 mutation was not associated with p53 expression detected by immunohistochemical staining with antibody 1801 or as p53 mRNA. In addition, events on 17p (allele losses, p53 mutation, p53 expression) were independent of c-erbB-2 expression. In breast cancer, by contrast with colorectal, lung and ovarian cancer, there appears to be no clear association between p53 DNA abnormalities and p53 expression.
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A total of 76 primary breast cancers were screened for p53 mutations using the yeast p53 functional assay, and the mutations were determined by DNA sequencing. Clonal mutations of p53 were detected in 30 tumors (39%). Immunohistochemical staining for nuclear p53 accumulation performed on the yeast a