Egr1 transcription factor: multiple roles in prostate tumor cell growth and survival

Abstract

The transcription factor, Egr1, so-called because it is encoded by the immediate early growth response gene, Egr1, is rapidly induced by growth factors to transduce the proliferative signal. The induction of Egr1 by external stimuli is generally transient but appears to be sustained in some prostate tumor cell lines and tumors, suggesting that Egr1 stimulates tumor cell growth. In contradiction, in breast, lung and brain tumors, Egr1 expression is often absent or reduced and when re-expressed, results in growth suppression. Re-expression of Egr1 in tumor cells also leads to antiapoptotic activity, which would encourage tumor cell survival. Egr1 is also required for, or stimulates, the differentiation of several cell types. Another contradiction is that after stress stimuli to some cell types, Egr1 is required for programmed cell death or apoptosis in both normal and tumor cells. Egr1 also plays a role in tumor progression, through the hypoxic signal generated in growing tumors. Egr1 is highly induced under these conditions and its activities stimulate angiogenesis and improved survival of tumor cells. How this large agenda can be achieved lies in the choice of Egr1 target genes, and varying patterns of coordinated expression have been described, but the mechanisms for this choice are not clear. This review points to areas where research should be focussed.