EGR1 target genes in prostate carcinoma cells identified by microarray analysis

The EGR1 transactivator is overexpressed in prostate cancer, and its expres sion pattern suggests that EGR1 could potentially regulate a number of step s involved in initiation and progression of prostate cancer, such as mitoge nesis, invasiveness, angiogenesis, and metastasis. To identify potential EG R1 target genes in an unbiased manner, we have utilized adenovirus-mediated expression of EGR1 in a prostate cancer cell line to identify specific gen es that are induced by EGR1. Using oligonucleotide arrays, a number of EGR1 -regulated genes were identified and their regulation was confirmed by quan titative reverse transcription-polymerase chain reaction analysis. One of t he largest gene classes identified in this screen includes several neuroend ocrine-associated genes (neuron-specific enolase, neurogranin), suggesting that EGR1 overexpression may contribute to the neuroendocrine differentiati on that often accompanies prostate cancer progression. This screen also ide ntified several growth factors such as insulin-like growth factor-II, plate let-derived growth factor-A, and transforming growth factor-beta1, which ha ve previously been implicated in enhancing tumor progression. The insulin-l ike growth factor-II gene lies within the 11p15.5 chromosomal locus, which contains a number of other imprinted genes, and EGR1 expression was found t o induce at least two other genes in this locus (IPL, p57(KIP2)). Based on our results, coupling adenoviral overexpression with microarray and quantit ative reverse transcription-polymerase chain reaction analyses could be a v ersatile strategy for identifying target genes of transactivators.