To identify estrogen-responsive genes in mammary glands, microarray assays were performed. Twenty genes were found to be upregulated while 16 genes were repressed in the 9 h estrogen treated glands. The induction of GAS6, one of the genes up-regulated by estrogen, was confirmed by RNase protection assay. Furthermore, GAS6 was also demonstrated to be induced by estrogen in ER positive breast cancer cells. Analysis of GAS6 promoter revealed that GAS6 promoter was regulated by estrogen. An estrogen response element (ERE) was identified in the GAS6 promoter. Electrophoretic mobility shift assay revealed that ER alpha interacted with the ERE in the GAS6 promoter. Chromatin immunoprecipitation demonstrated that ER alpha was recruited to the GAS6 promoter upon estrogen Stimulation. These results suggested that GAS6 is an estrogen target gene in mammary epithelial cells. (c) 2006 Elsevier Inc. All rights reserved.