Genes regulated by PCK Inhibitors, enzastaurin and Go, in CAL-27 cells, a SCCHN cell line

Efficacy of the Multi-Kinase Inhibitor Enzastaurin is Dependent on Cellular Signaling Context Testing a panel of SCCHN cell lines revealed variable sensitivity to enzastaurin which correlated significantly with baseline cyclin D1 protein expression. Moreover, sensitivity and resistance could be reversed, respectively, by expression or depletion of cyclin D1. Furthermore, analysis of sensitive and resistant cell lines revealed distinct differences in cyclin D1 regulation. Enzastaurin modulated cyclin D1 synthesis via an AKT regulated pathway in the former while high level CCND1 gene amplification was present in the latter. These results underscore the critical relevance of cellular signaling context in developing cancer therapies, in general, and suggest that enzastaurin, in particular, would be most effective in tumors where baseline cyclin D1 expression is low to moderate and physiologically regulated. CAL-27 cells were treated with the inhibitors for 24 hours and the gene expression from each group were analyzed