The human epidermal growth factor receptor-2 (HER2) plays an important role in breast cancer. Enhanced Ets-1 activity has recently been shown to be associated with breast cancer pathogenesis. To test the role of Ets-1 in breast cancer cells in relation to the expression of HER2 and MMP-1, we transiently overexpressed Ets-1 and/or HER2 in MCF-7 breast cancer cells and Comprehensively searched for genes related to HER2 and Ets-1 using cDNA microarray analysis. The expression of matrix rnetalloproteinase (MMP) genes was enhanced by the overexpression of HER2/Ets-1. We analyzed the relationship between HER2-induced MMP-1 expression and the transcription factor Ets-1, which has significant activity in breast cancer pathogenesis. Our results demonstrate that HER2-induced MMP-1 expression is positively regulated by Ets-1 in breast cancer cells. This study confirms that Ets-1 is a downstream effector of oncogenic HER2, associated with MMP-1. (C) 2008 Elsevier Inc. All rights reserved.