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 (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.
Yen
A
A
Cancer Biology Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853.
Coles
M
M
Varvayanis
S
S
D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002117:Calcitriol / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000166:cytology*; D009369:Neoplasms; D010587:Phagocytosis; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage*
D015214:Antigens, Differentiation, Myelomonocytic; D016760:Proto-Oncogene Proteins c-fos; D016160:Retinoblastoma Protein; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate