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Background  The transcription factor DEAF-1 has been identified as a high affinity binding partner of the LIM-only protein LMO4 that plays important roles in mammary gland development and breast cancer. Here we investigated the influence of DEAF-1 on human and mouse mammary epithelial cells both  in vitro  and  in vivo  and identified a potential target gene.    Results  Overexpression of DEAF-1 in human breast epithelial MCF10A cells enhanced cell proliferation in the mammary acini that develop in 3D cultures. To investigate the effects of Deaf-1 on mammary gland development and oncogenesis, we generated  MMTV-Deaf-1  transgenic mice. Increased ductal side-branching was observed in young virgin mammary glands, accompanied by augmented cell proliferation. In addition, the ratio of the progesterone receptor isoforms PRA and PRB, previously implicated in regulating ductal side-branching, was altered. Affymetrix gene profiling studies revealed  Rac3  as a potential target gene and quantitative RT-PCR analysis confirmed that  Rac3  was upregulated by Deaf-1 in immortalized mouse mammary epithelial cells. Furthermore,  MMTV-Deaf-1  transgenic mammary glands were found to have elevated levels of  Rac3  mRNA, suggesting that it is a  bona fide  target.    Conclusion  We have demonstrated that overexpression of  Deaf-1  enhances the proliferation of human breast epithelial cells  in vitro  and mouse epithelial cells  in vivo . Transgenic mammary glands overexpressing Deaf-1 exhibited a modest side-branching phenotype, accompanied by an increase in the number of BrdU-positive cells and a decrease in the proportion of PRA-expressing cells. Although proliferation was enhanced in Deaf-1 transgenic mice, overexpression of this gene was not sufficient to induce the formation of mammary tumors. In addition, our studies identified  Rac3 , encoding a small Rho-like GTPase, as a potential target of Deaf-1 in mouse mammary epithelial cells.

Deaf-1 regulates epithelial cell proliferation and side-branching in the mammary gland