In the September issue of the J. Clin. Investigation, E. L. McCoy et al. from the Univ. of Colorado Sch. of Medicine reported their study results on the role of the homeoprotein Six1 and mammary tumors. Six1 is a homeoprotein which is normally expressed during embryogenesis and downregulated in adult tissues. However, it appears that neoplastic cells overexpress Six1, particularly in breast tumors. With mammary-specific, inducible (tet-operator) Six1 transgenic mice, the investigators found that overexpression of Six1 leads to leads to aggressive mammary tumor formation that is dose-dependent (doxorubicin). Tumors were found to have diverse histologies of which a subset of sarcomatoid tumors undergoing epithelial-mesenchymal transition (EMT). Six1 driven tumors also displayed Wnt signaling which suggest that Six1 and Wnt primarly drives the malignant cells to an EMT state. Additionally, Six1 driven tumors contain cells expressing Sca-1 which seems to indicate a regulatory role for expanding the stem/progenitor pool in the mammary tissues by the transcription factor. Microarray analysis of human breast tumors resulted in low levels of Six1 gene expression concomitant with an increase in cyclin D1 expression. Thus, in human breast cancers, the authors proposed that Six1 in concert with cyclin D1 expression result in tumorigenesis of the mammary glands.