Retinoic acid differentiation of HL-60 cells promotes cytoskeletal polarization

Exp Cell Res. 2000 Jan 10;254(1):130-42. doi: 10.1006/excr.1999.4727.


Retinoic acid (RA) treatment of HL-60 cells in vitro induces granulocytic differentiation, involving reorganization of the nucleus and cytoplasm, development of chemoattractant-directed migration, and eventual apoptosis. The present studies with HL-60/S4 cells document that major elements of the cytoskeleton are changed: actin increases by 50%; vimentin decreases by more than 95%. The cellular content of alpha-tubulin does not significantly change; but the centrosomal-microtubule (MT) array moves away from the lobulating nucleus. Cytoskeletal-modifying chemicals modulate this polarized reorganization: Taxol and cytochalasin D enhance centrosome movement; nocodazole reverses it. Cytoskeletal-modifying chemicals do not appear to affect nuclear lobulation or the integrity of envelope-limited chromatin sheets (ELCS). Employing bcl-2-overexpressing HL-60 cells permitted demonstration of nuclear lobulation, ELCS formation, and centrosome-MT movement concomitantly during RA-induced differentiation, implying independence between the cellular reorganization and apoptotic programs. RA appears to promote an inherent potential in HL-60 cells for cytoskeletal polarization, likely to be important for chemoattractant-directed cell migration, an established characteristic of mature granulocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Apoptosis
  • Cell Differentiation
  • Cell Nucleus / drug effects
  • Centrosome / drug effects
  • Centrosome / metabolism
  • Cytochalasin D / pharmacology
  • Cytoskeleton / drug effects*
  • Cytoskeleton / metabolism
  • Cytoskeleton / physiology
  • HL-60 Cells / cytology
  • Humans
  • Interphase / drug effects
  • Mice
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Paclitaxel / pharmacology
  • Tretinoin / pharmacology*
  • Tubulin / metabolism
  • Vimentin / metabolism


  • Actins
  • Tubulin
  • Vimentin
  • Cytochalasin D
  • Tretinoin
  • Paclitaxel