Our scanning confocal microscopy seriously data show dif ferential localization of hornerin. Specifically, using anti bodies directed against the N terminus of hornerin we showed enhanced membrane staining and minimal nuclear localization, while nuclear localization was robustly evident when using an antibody directed against the C terminus. This Inhibitors,Modulators,Libraries differential subcellular localization of the fragments may suggest alternative functions for full length and fragmented hornerin. A similar mechan ism of subcellular localization of protein fragments was recently described for Ral binding protein 1, a protein implicated in Ras function, and other mul tiple functions localized to various subcellular regions including the nucleus, the actin cytoskeleton, and with the mitotic spindle and centrosome during mitosis.

Moreover, RalBP1 was shown to be proteolyzed into sev eral fragments with differential subcellular localization, suggesting the proteolyzed fragments mediated different cellular functions. Furthermore, differential subcellular localization of other S100 family members has been reported. Dis tinct intracellular localization of S100A6 and S100A4 was shown to be dependent on Inhibitors,Modulators,Libraries calcium concentrations in the MDA MB231 metastatic epithelial breast adeno carcinoma cells and cervical carcinoma HeLa cells. The authors propose the S100 Inhibitors,Modulators,Libraries proteins are involved in tumor cell calcium homeostasis. Additionally, S100A11 was shown to change from a strictly nuclear localization in normal breast tissue to a more cytoplasmic localiza tion in breast tumors.

The authors hypothesized that in normal breast S100A11 translocates to the nucleus which increases transcription of negative regulators of cell growth, while in cancer the loss of nuclear translocation may lead to an inability Inhibitors,Modulators,Libraries to control cell growth. Conclusion Our data highlight the potential role for hornerin, an S100 protein family member, in mammary cell function. We demonstrate hornerin expression in breast epithelial cells, stromal fibroblasts and macrophages, and show unique regulation of hornerin expression during distinct phases of mammary development. Furthermore, we show a decrease in hornerin expression in invasive ductal car cinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and altered cellular expression of hornerin during induction of apop tosis.

Finally, we demonstrate the presence of post translational fragments that display differential Inhibitors,Modulators,Libraries subcellular localization, which opens new inhibitor possibilities for the exist ence of fragment specific functions of hornerin. Background Oncogenic c Met signaling is widely implicated in various human malignancies. Upon binding to its ligand, hepato cyte growth factor, the c Met receptor initiates a signaling cascade leading to invasive growth and cancer cell dissemination.