Zebrafish: Estrogen induced gene expression

We performed microarray experiment on zebrafish exposed to estrogen (17β-estradiol; a classified carcinogen) and an anti-estrogen (ICI 182,780). Our transcriptome analysis captured multiple estrogen-responsive genes and signaling pathways that increased cell proliferation, promoted DNA damage and genome instability, and decreased tumor suppressing effects, suggesting a common mechanism for estrogen-induced carcinogenesis. Comparative analysis with human E2 responsive genes revealed a core set of conserved estrogen-responsive genes that demonstrate enrichment of ER binding sites and cell cycle signaling pathways. Knowledge-based and network analysis led us to propose that the mechanism involving estrogen-activated ER mediated down-regulation certain genes followed by up-regulation cell cycle-related genes is highly conserved. Our study provides first evidence of molecular conservation of estrogen-responsiveness between zebrafish and human cancer cell lines, hence demonstrating the potential of zebrafish for estrogen-related cancer research. 10 samples were analyzed in total. Three samples in control, 3 samples treated with estrogen and 3 samples treated with estrogen in combination with ICI.