title: Retinoic acid-induced CD38 expression in HL-60 myeloblastic leukemia cells regulates cell differentiation or viability depending on expression levels.
abstract: Retinoic acid-induced expression of the CD38 ectoenzyme receptor in HL-60 human myeloblastic leukemia cells is regulated by RARalpha and RXR, and enhanced or prevented cell differentiation depending on the level of expression per cell. RARalpha activation caused CD38 expression, as did RXR activation but not as effectively. Inhibition of MAPK signaling through MEK inhibition diminished the induced expression by both RARs and RXRs. Expression of CD38 enhanced retinoic acid-induced myeloid differentiation and G0 cell cycle arrest, but at higher expression levels, induced differentiation was blocked and retinoic acid induced a loss of cell viability instead. In the case of 1,25-dihydroxyvitamin D3, induced monocytic differentiation was also enhanced by CD38 and not enhanced by higher expression levels, but without induced loss of viability. Expression levels of CD38 thus regulated the cellular response to retinoic acid, either propelling cell differentiation or loss of viability. The cellular effects of CD38 thus depend on its expression level.
authors.affiliation: Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lamkin
authors.forename: Vivian
authors.initials: V
authors.lastname: Chin
authors.forename: Susi
authors.initials: S
authors.lastname: Varvayanis
authors.forename: James L
authors.initials: JL
authors.lastname: Smith
authors.forename: R Michael
authors.initials: RM
authors.lastname: Sramkoski
authors.forename: James W
authors.initials: JW
authors.lastname: Jacobberger
authors.forename: Andrew
authors.initials: A
authors.lastname: Yen
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014212:Tretinoin; D051997:ADP-ribosyl Cyclase 1