A phorbol diester resistant monocytic leukemia cell line is PKC deficient

MIA C51 is a rat monocytic leukemia cell line which exhibits undifferentiated monocytic phenotype in culture. The proliferation of MIA C51 cells was not inhibited by the addition of 12-O-tetradecanoyl-phorbol-13-acetate (TPA, 1 microgram/ml) or phorbol 12, 13 dibutyrate (PDBu, 10 micrograms/ml). Comparison of MIA C51 cells to a phorbol diester-sensitive human monoblastoid U-937 cell line demonstrated that MIA C51 cells contained significantly lower number of PDBu receptors, protein kinase C (PKC) activity, and PKC protein level. Further experiments demonstrated that addition of TPA to MIA C51 cells did not induce the expression of c-fos proto-oncogene; whereas incubation of MIA C51 cells with N6, O2-dibutyryl cyclic adenosine 3',5' monophosphate (Bt2cAMP) resulted in a rapid increase of c-fos mRNA level. Thus, this cell line provides a new system for studying the signal transduction mechanisms in induced monocytic differentiation.