title: LIF-induced STAT3 signaling in murine versus human embryonal carcinoma (EC) cells.
abstract: Self-renewal and the maintenance of pluripotency of mouse embryonal stem (ES) cells in vitro requires exogenous leukemia inhibitory factor (LIF). Mouse ES cells can be cultured and kept undifferentiated in the absence of embryonal feeder-cell layers when exogenous LIF concentrations are maintained above a threshold concentration. An important downstream target of LIF signal transduction in mouse ES cells is the transcription factor signal transducer and activator of transcription 3 (STAT3). In contrast to mouse ES cells, human ES cells are unresponsive to LIF and depend on feeder cells for undifferentiated growth. Here, we investigated the activation patterns of LIF-downstream effectors in mouse and human embryonal carcinoma (EC) cells. We report that LIF induces both ERK-1 as well as STAT3 activation in mouse P19 EC cells. LIF enhances the proliferation rate of P19 EC cells, which depends on ERK activity but does not require activation of STAT3. In contrast, LIF does not activate STAT3, ERK, or the gp130 receptor in human N tera-2/D1 EC cells, although all receptor components are expressed. The negative feedback protein suppressor of cytokine signaling 1 (SOCS-1) is constitutively expressed in N tera-2/D1 EC cells, suggesting that LIF signal transduction is inhibited by elevated levels of SOCS-1 expression.
authors.affiliation: Department of Developmental Genetics, Biological Center, Kerklaan 30, Haren, 9751 NN, The Netherlands
authors.forename: Jan Jacob
authors.initials: JJ
authors.lastname: Schuringa
authors.forename: Saskia
authors.initials: S
authors.lastname: van der Schaaf
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Bart J L
authors.initials: BJ
authors.lastname: Eggen
authors.forename: Wiebe
authors.initials: W
authors.lastname: Kruijer
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D018243:Teratocarcinoma / Q000473:pathology; D015534:Trans-Activators / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D008562:Membrane Glycoproteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C491590:Socs1 protein, mouse; C494087:Stat3 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D050822:Cytokine Receptor gp130; D020928:Mitogen-Activated Protein Kinases