title: Prostacyclin receptor-dependent inhibition of human erythroleukemia cell differentiation is STAT3-dependent.
abstract: We have previously demonstrated that activation of prostacyclin (IP) receptors in human erythroleukemia (HEL) cells phosphorylates the signal transducer and activator of transcription 3 (STAT3) via Gα(s) and Gα(16) hybrid signalling. This current study was designed to determine if functional responses to cicaprost in HEL cells were dependent on STAT3 phosphorylation. Cicaprost significantly enhanced the rapid change in HEL cell morphology induced by phorbol-12-myristate-13-acetate (PMA), and this effect was inhibited by the IP receptor antagonist RO1138452 and a STAT3 inhibitory peptide. Other indicators of PMA-induced HEL cell differentiation, such as increased expression of CD41/CD61 and an increase in cell complexity/granularity, were inhibited by cicaprost in an IP receptor-dependent and STAT3-dependent manner. Although thrombopoietic cytokines promote megakaryocytic differentiation and platelet production via activation of STAT3, the predominant STAT3-dependent effects of cicaprost in HEL cells were inhibitory towards the process of PMA-induced megakaryocytopoeisis.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China.
authors.forename: Alaster H Y
authors.initials: AH
authors.lastname: Lau
authors.forename: Henry K H
authors.initials: HK
authors.lastname: Lai
authors.forename: Barry H S
authors.initials: BH
authors.lastname: Yeung
authors.forename: Sze Lee
authors.initials: SL
authors.lastname: Leung
authors.forename: Suk Ying
authors.initials: SY
authors.lastname: Tsang
authors.forename: Yung H
authors.initials: YH
authors.lastname: Wong
authors.forename: Helen
authors.initials: H
authors.lastname: Wise
mesh_terms: D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000473:pathology*; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism / Q000494:pharmacology; D044006:Receptors, Epoprostenol / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: C061248:ITGB3 protein, human; D039661:Integrin beta3; D040201:Platelet Membrane Glycoprotein IIb; D044006:Receptors, Epoprostenol; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D011464:Epoprostenol; C043867:cicaprost; D013755:Tetradecanoylphorbol Acetate