Platelet-derived growth factor receptor regulates myeloid and monocytic differentiation of HL-60 cells.
Here, we show that the platelet-derived growth factor receptor (PDGFR) regulates myeloid and monocytic differentiation of HL-60 myeloblastic leukemia cells in response to retinoic acid (RA) and vitamin D3 (D3), respectively. Both RA and D3 decreased the expression of PDGFR-alpha and PDGFR-beta throughout differentiation. When cells were treated with the PDGFR inhibitor AG1296 in addition to RA or D3, signs of terminal differentiation such as inducible oxidative metabolism and cell substrate adhesion were enhanced. These changes were accompanied by an increased extracellular signal-regulated kinase 1/2 activation. AG1296 also resulted in elevated expression of differentiation markers CD11b and CD66c when administered with RA or D3. Interestingly, other markers did not follow the same pattern. Cells receiving AG1296 in addition to RA or D3 showed decreased G1-G0 arrest and CD14, CD38, and CD89 expression. We thus provide evidence that certain sets of differentiation markers can be enhanced, whereas others can be inhibited by the PDGFR pathway. In addition, we found calcium levels to be decreased by RA and D3 but increased when AG1296 was given in addition to RA or D3, suggesting that calcium levels decrease during myeloid or monocytic differentiation, and elevated calcium levels can disturb the expression of certain differentiation markers.
Reiterer
Gudrun
G
Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853, USA.
Yen
Andrew
A
D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D015703:Antigens, CD / Q000096:biosynthesis; D039481:CD11b Antigen / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002454:Cell Differentiation; D002762:Cholecalciferol / Q000494:pharmacology; D058851:GPI-Linked Proteins; D018922:HL-60 Cells; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D011961:Receptors, Fc / Q000096:biosynthesis; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology; D025801:Ubiquitin / Q000378:metabolism
D015703:Antigens, CD; D039481:CD11b Antigen; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; C036832:Fc(alpha) receptor; D058851:GPI-Linked Proteins; C509295:ITGAM protein, human; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011961:Receptors, Fc; D020032:Tyrphostins; D025801:Ubiquitin; C106250:6,7-dimethoxy-3-phenylquinoxaline; D002762:Cholecalciferol; D014212:Tretinoin; D017479:Receptors, Platelet-Derived Growth Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium