TUMOR-GROWTH AND CELL-KINETICS IN VARIANTS OF A HUMAN ENDOMETRIAL ADENOCARCINOMA EXPRESSING EITHER WILD-TYPE OR MUTANT P53

We have compared the baseline cell proliferation and tumour growth in two variants of a human endometrial adenocarcinoma grown in nude mice. One of these tumour variants expressed wild-type p53 whereas the othe r had mutations of the p53 gene at codon 175 in both alleles and at co don 248 in one allele. There was no difference in growth rate between the tumour variants. Cell proliferation parameters, such as labelling index and S-phase fraction, were significantly increased in the tumour with mutated p53 and consequently there was a significantly lower pro portion of cells in the G1-phase, proposing an at least partial loss o f suppressor function in this tumour. Semi-quantitative analysis of th e p53 and bcl-2 proteins showed a significant overexpression of p53 an d a decreased expression of the bcl-2 protein in the p53 mutated tumou r variant compared with the variant with wild-type p53. We conclude th at wild-type p53 protein acts as an active suppressor in the regulatio n of the baseline growth and cell kinetics of this tumour and could be linked through a p53-bcl-2 system in human endometrial adenocarcinoma s.