Inhibition of protein kinase C δ has negative effect on anchorage-independent growth of BCR-ABL-transformed Rat1 cells

Abstract 

The BCR-ABL oncoprotein transmits transformation signals mainly through pathways involving Ras, Myc and PI3 kinase. Here we report that inhibition of protein kinase C (PKC) δ had negative influence on anchorage-independent growth of Rat1 cells transformed by BCR-ABL. The effect was observed with δ isoform-specific inhibitor rottlerin, but not with Go6976 that inhibits only conventional isoforms. The kinase activity of δ isoform was found to be roughly two-fold higher in BCR-ABL-expressing Rat1 cells than that in mock. Although overexpression of wild type PKC δ did not enhance soft agar colony number by BCR-ABL-transformed Rat1 cells, that of dominant-negative δ isoform reduced it by approximately 40%.

Keywords: BCR-ABL, Tyrosine kinase, Oncogene, Transformation, Protein kinase C