PEA3 transcription factors are expressed in tissues undergoing branching morphogenesis and promote formation of duct-like structures by mammary epithelial cells in vitro.

The genetic program that controls reciprocal tissue interactions during epithelial organogenesis is still poorly understood. Erm, Er81 and Pea3 are three highly related transcription factors belonging to the Ets family, within which they form the PEA3 group. Little information is yet available regarding the function of these transcription factors. We have previously used in situ hybridization to compare their expression pattern during critical stages of murine embryogenesis [Oncogene 15 (1997), 937; Mech. Dev. 108 (2001), 191]. In this study, we have examined the expression of PEA3 group members during organogenesis of the lung, salivary gland, kidney, and mammary gland. In all of these developmental settings, we observed a tight correlation between branching morphogenesis and the expression of specific members of the PEA3 group. To assess the functional relevance of these findings, Erm and Pea3 were overexpressed in the TAC-2.1 mammary epithelial cell line, which has the ability to form branching duct-like structures when grown in collagen gels. We found that overexpression of Erm and Pea3 markedly enhances branching tubulogenesis of TAC-2.1 cells and also promotes their invasion into a collagen matrix. Collectively, these findings suggest that the differential expression of PEA3 group transcription factors has an important role in the regulation of branching morphogenesis and raise the question of their implication in branching signaling.