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Growth control or terminal differentiation: endogenous production and differential activities of vitamin A metabolites in HL-60 cells.

Abstract
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.
AuthorsT M Eppinger, J Buck, U Hämmerling
JournalThe Journal of experimental medicine (J Exp Med) Vol. 178 Issue 6 Pg. 1995-2005 (Dec 01 1993) ISSN: 0022-1007 [Print] United States
PMID8245778 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Diterpenes
  • Growth Inhibitors
  • Retinoids
  • Vitamin A
  • 14-hydroxy-4,14-retro-retinol
  • anhydrovitamin A
  • Tretinoin
Topics
  • Cell Differentiation (drug effects)
  • Cell Division (drug effects)
  • Diterpenes
  • Granulocytes (cytology)
  • Growth Inhibitors
  • Humans
  • In Vitro Techniques
  • Retinoids (metabolism)
  • Tretinoin (pharmacology)
  • Tumor Cells, Cultured
  • Vitamin A (analogs & derivatives, pharmacology)

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