p53 messenger RNA expression was examined using a cDNA probe in 76 fresh primary breast tumour specimens, 15 of which came from patients treated with taxoxifen prior to surgery. A 2.8 kb mRNA for p53 was expressed in 43 of the 76 specimens. In 19 tumours the levels were similar to those seen in non-malignant (reduction mammoplasty) breast tissue, but in 24 tumours over-expression of mRNA for p53, approaching that seen in three breast cancer cell lines, was found. The cell lines MCF-7, T47D and MDA-MB-231 expressed three p53 mRNA species of about 2.8 kb and a fourth of 1.6 kb. Increased mRNA expression for p53 correlated (P <0.05) with loss of genetic material from the short arm of chromosome 17 as demonstrated by allele loss with the VNTR probe YNZ 22.1. There was also statistically significant correlation between increased p53 mRNA expression and low oestrogen receptor protein content in the tumours (P <0.05), but not with other clinical parameters. The findings support the view that p53 is involved in breast tumour biology, and suggest that its role may be complex. p53 is a 53 kDa phosphoprotein with a short half-life role of p53 protein remains obscure although the p53 gene has the structural features of a 'housekeeping' gene, including absence of a TATA box (Reynolds et al., 1984; Bienz-Tadmor et al., 1985). p53 may modulate transcriptional activation by binding to DNA in a similar way to the myc protein (Donner et al., 1982), allowing cells to progress from a growth arrested state to an actively dividing state or to bypass the need for platelet derived growth factor in the induction of competence (Oren, 1986). Despite persuasive evidence for its role as an oncogene there is also reason to believe that p53 can act as a tumour suppressor gene (Green, 1989; Wang et al., 1989). This paradox may be resolved if rearrangements of the p53 DNA alter the structure, expression (Masuda et al., 1987) or stability (Jenkins et al., 1985) of the 53 kDa protein product and if the function of a mutated p53 product differs from that of the normal gene (Green, 1989). The p53 gene maps to the 13.1 region of the short arm of chromosome 17 (Miller et al., 1986). One previous study (Masuda et al., 1987) did not find detectable changes in the p53 gene in breast cancer. However, using the YNZ 22.1 probe (Nakamura et …
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- Publication year
2002
- Venue
International Journal of Integrated Care
- Publication date
2002-04-01
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