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Title: Human myeloblastic leukemia cells (HL-60) express a membrane receptor for estrogen that signals and modulates retinoic acid-induced cell differentiation

Estrogen receptors are historically perceived as nuclear ligand activated transcription factors. An estrogen receptor has now been found localized to the plasma membrane of human myeloblastic leukemia cells (HL-60). Its expression occurs throughout the cell cycle, progressively increasing as cells mature from G{sub 1} to S to G{sub 2}/M. To ascertain that the receptor functioned, the effect of ligands, including a non-internalizable estradiol-BSA conjugate and tamoxifen, an antagonist of nuclear estrogen receptor function, were tested. The ligands caused activation of the ERK MAPK pathway. They also modulated the effect of retinoic acid, an inducer of MAPK dependent terminal differentiation along the myeloid lineage in these cells. In particular the ligands inhibited retinoic acid-induced inducible oxidative metabolism, a functional marker of terminal myeloid cell differentiation. To a lesser degree they also diminished retinoic acid-induced earlier markers of cell differentiation, namely CD38 and CD11b. However, they did not regulate retinoic acid-induced G{sub 0} cell cycle arrest. There is thus a membrane localized estrogen receptor in HL-60 myeloblastic leukemia cells that can cause ERK activation and modulates the response of these cells to retinoic acid, indicating crosstalk between the membrane estrogen and retinoic acid evoked pathways relevant to propulsion of cell differentiation.
Authors:
; ;  [1] ;  [2]
  1. Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853 (United States)
  2. Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853 (United States), E-mail: ay13@cornell.edu
Publication Date:
OSTI Identifier:
21128158
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 314; Journal Issue: 16; Other Information: DOI: 10.1016/j.yexcr.2008.07.015; PII: S0014-4827(08)00295-4; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BLOOD CELLS; CELL CYCLE; CELL DIFFERENTIATION; ESTRADIOL; HEMOLYSIS; LEUKEMIA; LIGANDS; OXIDATION; RECEPTORS; RETINOIC ACID; SAPONINS; TAMOXIFEN; TRANSCRIPTION FACTORS