Pro-inflammatory mediator leukotriene D4 induces transcriptional activity of potentially oncogenic genes.

The inflammatory mediator LTD 4 (leukotriene D 4 ) is present at high levels in many inflammatory conditions, and areas of chronic inflammation have an increased risk for subsequent cancer development. We demonstrate here that following LTD 4 stimulation, β-catenin is translocated to the nucleus, triggering the transcriptional activity of the TCF (T-cell factor)/LEF (lymphoid enhancer factor) family of transcription factors. These events are dependent on phosphoinositide-3 kinase activation and glycogen synthase kinase inhibition. Our data suggest that, similar to Wnt signalling, LTD 4 increases free β-catenin and targets it to the nucleus.