A. Immunohistochemical staining of human mammary tissues. The expression of TSHZ2, CtBP2, GLI1, CXCR4 and AEBP1 was evaluated by staining intensity and semi-quantitatively scored (negative, 0; weak, 1; moderate, 2; strong, 3) as indicated in the photos. Bar, 20 μm. B. Correlation of TSHZ2 expression with AEBP1, CXCR4 and GLI1 expression. C. Correlation of TSHZ2 expression with the subcellular distribution of GLI1. D. A schematic of the proposed mechanism for GLI1 activation during mammary tumorigenesis. In normal mammary gland duct epithelium, GLI1 is sequestered in nucleus and its transcriptional activity is suppressed by the TSHZ2-CtBP2 repressor complex. During tumorigenesis, TSHZ2 is down-regulated, and in turn, GLI1 is released from the TSHZ2-containing repressor complex and is shuttled between subcellular compartments, thereby enabling the transactivation of target gene expression.