Direct transcriptional regulation of MDM2 by Fli-1.

The Ets transcription factor, Fli-1, has been shown to play a pivotal role in the induction and progression of Friend Murine Leukemia Virus (F-MuLV)-induced erythroleukemia, with its overexpression leading to erythroblast survival, proliferation, and inhibition of terminal differentiation. P53 inactivation is an additional genetic alteration that occurs in late-stage leukemic progression associated with in vivo and in vitro immortalization. Since p53 protein expression levels are low, to undetectable, in primary erythroleukemic cells that express elevated levels of Fli-1, we investigated the potential regulation of p53 by Fli-1.

Phosphorylation status of c-Kit and Epo receptors, and the presence of wild-type p53 confer in vitro resistance of murine erythroleukemic cells to Celecoxib.

It is well established that selective COX-2 inhibitors exhibit potent effects against progression of select solid tumours. However, their effects on liquid tumours have not been fully established. By taking advantage of murine Friend Disease we have shown a strong antileukemic effect of celecoxib by determining novel in vitro targets.