Growth control or terminal differentiation: endogenous production and differential activities of vitamin A metabolites in HL-60 cells.
Vitamin A (retinol) is a prohormone that exerts its pleiotropic biological effects after conversion into multiple metabolites. In this report we describe the identification of three endogenous, retinolderived effector molecules, 14-hydroxy-retro-retinol (14-HRR), anhydroretinol (AR), and retinoic acid (RA) and a putative storage form of retinol, retinylesters (RE) in the human promyelocytic leukemia cell line HL-60. Exogenous application of the retinol metabolites in retinol-depleted serum-free cultures of HL-60 allowed the identification of unique cellular functions for each metabolite: 14-HRR is a growth factor for HL-60. AR is a functional antagonist of 14-HRR with growth-inhibiting activity, and RA is a potent inducer of granulocyte differentiation accompanied by growth arrest. Finally, intracellular RE serves as storage form allowing continuous production of 14-HRR when no external retinol is available.
Eppinger
T M
TM
Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York.
Buck
J
J
Hämmerling
U
U
D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D004224:Diterpenes; D006098:Granulocytes / Q000166:cytology; D006131:Growth Inhibitors; D006801:Humans; D066298:In Vitro Techniques; D012176:Retinoids / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014801:Vitamin A / Q000031:analogs & derivatives / Q000494:pharmacology*
D004224:Diterpenes; D006131:Growth Inhibitors; D012176:Retinoids; D014801:Vitamin A; C072014:14-hydroxy-4,14-retro-retinol; C031469:anhydrovitamin A; D014212:Tretinoin