1,25‐dihydroxy vitamin D3 and 12‐O‐tetradecanoyl phorbol‐13‐acetate synergistically induce monocytic cell differentiation: FOS and RB expression

Abstract

1,25-dihydroxy vitamin D3 and 12-O-tetradecanoyl phorbol-13-acetate (TPA) interact synergistically to induce monocytic differentiation of U937 histiocytic lymphoma cells. Addition of TPA causes an otherwise ineffective dose of 1,25-dihydroxy vitamin D3 to induce differentiation. The induced differentiation depends on the simultaneous (vs. sequential) presence of both agents. The kinetics of induced differentiation are consistent with a G1 specific cellular response to initiate the metabolic cascade culminating in cell differentiation. The induced differentiation occurs with down-regulation of c-fos protein and an accompanying up-regulation of RB protein expression, consistent with a possible need for up-regulated RB expression to maintain a given differentiated phenotype and suppress transcriptional activators that might typically be associated with proliferation.

True

“…In U937 lymphoma cells, cell differentiation induced by 1␣,25(OH) 2 D 3 and PMA was assumed to be dependent on PKC-mediated phosphorylation of VDR. 42 Activation of different PKC isoforms by 1␣,25(OH) 2 D 3 and PMA was also proposed as a mechanism in the differentiation of THP-1 leukemia cells and NB4 cells. 43,44 We have already reported that in NB4 cells, mitogen-activated protein kinase is involved in 1␣,25(OH) 2 D 3 action.…”