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Abstract Background The Wnt/Wg pathway plays an important role in the developmental program of many cells and tissues in a variety of organisms. In addition, many Wnts and components of their downstream signaling pathways, such as β-catenin and APC, have been implicated in tumorigenesis. Over the past years, several genes have been identified as Wnt responsive, including <it>c-myc</it>, <it>siamois</it>, and <it>cyclin D1</it>. Results In order to identify additional genes responsive to Wnt signaling that contribute to the transformed phenotype, we performed a cDNA subtractive hybridization screen between a mouse mammary epithelial cell line that overexpresses <it>Wnt-1 </it>(C57MG/Wnt-1) and the parental cell line (C57MG). The screen identified a total of 67 genes to be up-regulated in response to Wnt signaling. Of these 67 genes, the up-regulation of 62 was subsequently confirmed by Northern and dot blot analyses (and, for a subset, semi-quantitative PCR) of RNA isolated from C57MG cells subjected to (1) an independent Wnt-1 retroviral infection, and (2) co-culture with Wnt-1 expressing cells. Among the confirmed Wnt-1 responsive genes, we further characterized a mouse homolog of the human transcription factor Basic Transcription Element Binding protein 2 (<it>BTEB2</it>), Wnt-1 Responsive Cdc42 homolog (<it>Wrch-1</it>), and Wnt-1 Induced Secreted Protein (<it>WISP-1</it>). Conclusion Several novel genes were identified in this screen, as well as others that have been shown previously to be regulated by Wnt signaling, such as <it>connexin43</it>. The results indicate that cDNA subtractive hybridization is a useful method for identifying genes involved in the process of Wnt-1-induced transformation.</p

Identification of Wnt responsive genes using a murine mammary epithelial cell line model system