Expression of p53 in urothelial cell cultures from tumour-bearing and tumour-free patients.
An explant culture technique was used to culture normal urothelium from patients with muscle-invasive bladder cancer (transitional cell carcinoma, TCC) (n = 11) and from non-tumour-bearing patients (n = 60). Cell cultures were examined for expression of p53 using the monoclonal antibody p53-240. There was a statistically significant increase in p53 expression in normal urothelial cell cultures from patients with TCC (P < 0.0005). Normal urothelial cultures from patients with TCC also showed more rapid proliferation in vitro when compared with non-tumour-bearing patients (P < 0.0005). A subgroup of non-tumour-bearing patients (n = 14) showed > 5% of cells expressing p53. p53 expression in this subgroup was found to correlate with cell proliferation in vitro (r2 = 0.766). None of these urothelial specimens was observed to express p53 when paraffin-embedded preparations were stained with p53-D07 antibody prior to culture. The rate of cellular proliferation in this subgroup did not differ from that of normal urothelium from TCC patients. Twenty-two paraffin-embedded, muscle-invasive TCC specimens were also evaluated for p53 expression using p53-D07. The expression of p53 in these tumours did not differ from that observed in normal urothelial cell cultures from patients with TCC (P = 0.26). This study identifies an overexpression of p53 in normal urothelial cells from patients with TCC and in proliferating cultures from a significant subgroup of patients without malignant disease. Increased p53 expression in normal cultured urothelial cells from patients with bladder cancer implies a global change in the mechanisms controlling urothelial cell division. This may represent an early step in the pathway to carcinogenesis.
Harney
J
J
Department of Urology, Royal University Hospital, Liverpool, UK.
Murphy
D M
DM
Jones
M
M
Mothersill
C
C
D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000473:pathology; D002478:Cells, Cultured; D006801:Humans; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D001743:Urinary Bladder / Q000737:chemistry* / Q000166:cytology; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000473:pathology
D016159:Tumor Suppressor Protein p53