Abstract:
Interferon-γ (IFNG) is a cytokine that exerts potent antiproliferative and tumoricidal effects in a variety of cancers. Moreover, IFNG modulates normal pituitary hormone secretion, and was shown to inhibit the expression of the ACTH precursor POMC in murine ACTH-secreting AtT-20 tumor cells. We have studied the functional role of IFNG on pituitary tumor cells, focusing on the involvement of IFNG in the molecular events leading to the control of POMC transcriptional repression. Herein, it is shown that IFNG inhibits AtT-20 tumor cell proliferation without inducing apoptosis. Unexpectedly, an activated janus kinases-signal transducer and activator of transcription (JAK-STAT1) cascade is required for IFNG inhibitory action on POMC promoter activity. Factor-kappa B (NF-κB) is necessary for the inhibitory action of IFNG on Pomc transcription, since loss of NF-κB activity with IκB super-repressor abolishes this effect. In addition, 1 and 2 IFNG receptor immunoreactivity was detected in human corticotropinoma cells. Interestingly, IFNG inhibits ACTH production from these cells in primary cell culture, without affecting basal ACTH biosynthesis in normal non-tumoral pituitary cells. In conclusion, our data show for the first time that POMC transcription can be negatively regulated by a JAK-STAT1 and NF-KB-dependent pathway. © 2008 Society for Endocrinology.
Registro:
Documento: |
Artículo
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Título: | Interferon-γ inhibits cellular proliferation and ACTH production in corticotroph tumor cells through a novel janus kinases-signal transducer and activator of transcription 1/nuclear factor-kappa B inhibitory signaling pathway |
Autor: | Labeur, M.; Refojo, D.; Wölfel, B.; Stalla, J.; Vargas, V.; Theodoropoulou, M.; Buchfelder, M.; Paez-Pereda, M.; Arzt, E.; Stalla, G.K. |
Filiación: | Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Munich 80804, Germany Department of Molecular Neurogenetics, Max Planck Institute of Psychiatry, Munich 80804, Germany Department of Inflammatory Disorders of the CNS, Max Planck Institute of Psychiatry, Munich 80804, Germany Department of Neurosurgery, University of Erlangen, Erlangen 91054, Germany Department of Affectis Pharmaceuticals, Munich 82152, Germany Laboratorio de Fisiología y Biología Molecular, University of Buenos Aires, CONICET, Buenos Aires 1428, Argentina
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Palabras clave: | corticotropin; gamma interferon; gamma interferon receptor; gamma interferon receptor 1; gamma interferon receptor 2; immunoglobulin enhancer binding protein; Janus kinase; proopiomelanocortin; STAT1 protein; unclassified drug; ACTH secreting adenoma; animal cell; article; cell proliferation; controlled study; corticotropin release; Cushing disease; gene expression regulation; gene repression; hormone synthesis; human; human cell; human tissue; hypophysis cell; mouse; nonhuman; priority journal; promoter region; regulatory mechanism; signal transduction; transcription regulation; Adrenocorticotropic Hormone; Animals; Blotting, Western; Cell Proliferation; Humans; Interferon-gamma; Janus Kinases; Mice; NF-kappa B; Pituitary Neoplasms; Pro-Opiomelanocortin; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; STAT1 Transcription Factor; Transcription, Genetic |
Año: | 2008
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Volumen: | 199
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Número: | 2
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Página de inicio: | 177
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Página de fin: | 189
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DOI: |
http://dx.doi.org/10.1677/JOE-08-0011 |
Título revista: | Journal of Endocrinology
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Título revista abreviado: | J. Endocrinol.
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ISSN: | 00220795
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CODEN: | JOENA
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CAS: | Janus kinase, 161384-16-3; corticotropin, 11136-52-0, 9002-60-2, 9061-27-2; gamma interferon, 82115-62-6; proopiomelanocortin, 66796-54-1; Adrenocorticotropic Hormone, 9002-60-2; Interferon-gamma, 82115-62-6; Janus Kinases, 2.7.1.112; NF-kappa B; Pro-Opiomelanocortin, 66796-54-1; STAT1 Transcription Factor
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00220795_v199_n2_p177_Labeur |
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Citas:
---------- APA ----------
Labeur, M., Refojo, D., Wölfel, B., Stalla, J., Vargas, V., Theodoropoulou, M., Buchfelder, M.,..., Stalla, G.K.
(2008)
. Interferon-γ inhibits cellular proliferation and ACTH production in corticotroph tumor cells through a novel janus kinases-signal transducer and activator of transcription 1/nuclear factor-kappa B inhibitory signaling pathway. Journal of Endocrinology, 199(2), 177-189.
http://dx.doi.org/10.1677/JOE-08-0011---------- CHICAGO ----------
Labeur, M., Refojo, D., Wölfel, B., Stalla, J., Vargas, V., Theodoropoulou, M., et al.
"Interferon-γ inhibits cellular proliferation and ACTH production in corticotroph tumor cells through a novel janus kinases-signal transducer and activator of transcription 1/nuclear factor-kappa B inhibitory signaling pathway"
. Journal of Endocrinology 199, no. 2
(2008) : 177-189.
http://dx.doi.org/10.1677/JOE-08-0011---------- MLA ----------
Labeur, M., Refojo, D., Wölfel, B., Stalla, J., Vargas, V., Theodoropoulou, M., et al.
"Interferon-γ inhibits cellular proliferation and ACTH production in corticotroph tumor cells through a novel janus kinases-signal transducer and activator of transcription 1/nuclear factor-kappa B inhibitory signaling pathway"
. Journal of Endocrinology, vol. 199, no. 2, 2008, pp. 177-189.
http://dx.doi.org/10.1677/JOE-08-0011---------- VANCOUVER ----------
Labeur, M., Refojo, D., Wölfel, B., Stalla, J., Vargas, V., Theodoropoulou, M., et al. Interferon-γ inhibits cellular proliferation and ACTH production in corticotroph tumor cells through a novel janus kinases-signal transducer and activator of transcription 1/nuclear factor-kappa B inhibitory signaling pathway. J. Endocrinol. 2008;199(2):177-189.
http://dx.doi.org/10.1677/JOE-08-0011