ESTRADIOL INDUCES DNA FRAGMENTATION IN A HUMAN ENDOMETRIAL ADENOCARCINOMA WITH ESTRADIOL-INHIBITED GROWTH PHENOTYPE

A moderately differentiated human endometrial adenocarcinoma heterotra nsplanted into nude mice was investigated for morphological and molecu lar changes in the tumours after treating the animals with estradiol. The tumour growth was previously characterised as estradiol-independen t but responsive (inhibited) without any changes in cell proliferation . In response to hormonal treatment rather the cell loss factor increa sed. In this experiment tumours influenced by estradiol were investiga ted at different time-points after treatment by an in situ labelling t echnique to detect cells undergoing DNA fragmentation as a sign of apo ptosis. Expression of the apoptosis related protein bcl-2 was evaluate d by Western blotting. Tumours from animals treated with estradiol sho wed an increase in armour volume doubling time from 5.4 days to 16 day s compared to control tumours. Histologically, tumours influenced by e stradiol were better differentiated than control tumours and showed a significant increase in cells staining positively with the in situ apo ptosis detection technique. A parallel time dependent decreased expres sion of bcl-2 protein was observed. These results confirm our previous findings where estradiol influenced the cell loss factor without chan ges in the growth fraction indicating increased apoptotic activity in response to hormonal treatment.