1,25-DIHYDROXY VITAMIN-D3 AND 12-O-TETRADECANOYL PHORBOL-13-ACETATE SYNERGISTICALLY INDUCE MONOCYTIC CELL-DIFFERENTIATION - FOS AND RB EXPRESSION

1,25-dihydroxy vitamin D3 and 12-O-tetradecanoyl phorbol-13-acetate (T PA) interact synergistically to induce monocytic differentiation of U9 37 histiocytic lymphoma cells. Addition of TPA causes an otherwise ine ffective dose of 1,25-dihydroxy vitamin D3 to induce differentiation. The induced differentiation depends on the simultaneous (vs. sequentia l) presence of both agents. The kinetics of induced differentiation ar e consistent with a G1 specific cellular response to initiate the meta bolic cascade culminating in cell differentiation. The induced differe ntiation occurs with down-regulation of c-fos protein and an accompany ing up-regulation of RB protein expression, consistent with a possible need for up-regulated RB expression to maintain a given differentiate d phenotype and suppress transcriptional activators that might typical ly be associated with proliferation. (C) 1993 Wiley-Liss, Inc.