linked to SWI/ SNF complexes to promote changes in gene expression that may be critical for tumor cell invasion. SCAI is a transcriptional repressor of SRF and a highly conserved protein among vertebrates. The protein expression of SCAI in native human tissues and its sub-cellular localization have not yet been determined. Here, we investigated levels of protein expression of SCAI in a wide range of normal human tissues. By Western blot analysis we detected expression of SCAI in all normal tissues, except for spleen, with highest levels of expression in colon and gallbladder. Our previous studies on tissue culture cells demonstrated that SCAI is mainly expressed in the nucleus. To determine the subcellular localization of SCAI in native tissue, we ABT-737 stained sections of normal breast tissue. We show that the expression of SCAI is restricted to the duct epithelia of the mammary gland, mainly expressed in the nucleus. Our initial data revealed that SCAI expression is diminished at the RNA-level in many human malignancies including breast cancer. To further substantiate these findings, we have analyzed a large panel of primary human breast tumors by western blot for SCAI expression. Compared to normal breast tissue, we observed a decrease of SCAI expression in all tumor samples analyzed, supporting our initial finding that downregulation of SCAI may be linked to tumorigenesis. However, we did not observe a correlation between the breast cancer stage and the reduction of SCAI protein levels, suggesting that downregulation of SCAI is an early event in tumorigenesis and is not associated with tumor progression. As control for our data set, we analyzed the abundance of RhoC, and found that enhanced expression of RhoC occurs mainly in late stage tumors, which is in agreement with a publication by Kleer et al.. However, the question of how SCAI impacts on gene regulation at a molecular level as well as the link between SCAI expression and tumor development is at present not fully understood. SCAI does neither share any sequence homologies to other known proteins nor any predicted domain architecture or intrinsic catalytic activity. Therefore, it seemed tempting to speculate that SCAI could serve as an adapter protein that recruits ABT-267 biological activity chromatin modifying enzymes, like Histone Deacetylases, Methytransferases, or ATP-utilizing chromatin remodeling enzymes to specific genomic regions and thereby controls expression of target genes. To identify the molecular link be