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
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...
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todo:paper_00220795_v199_n2_p177_Labeur2023-10-03T14:25:56Z 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 Labeur, M. Refojo, D. Wölfel, B. Stalla, J. Vargas, V. Theodoropoulou, M. Buchfelder, M. Paez-Pereda, M. Arzt, E. Stalla, G.K. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00220795_v199_n2_p177_Labeur |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Labeur, M. Refojo, D. Wölfel, B. Stalla, J. Vargas, V. Theodoropoulou, M. Buchfelder, M. Paez-Pereda, M. Arzt, E. Stalla, G.K. 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Labeur, M. Refojo, D. Wölfel, B. Stalla, J. Vargas, V. Theodoropoulou, M. Buchfelder, M. Paez-Pereda, M. Arzt, E. Stalla, G.K. |
| author_facet |
Labeur, M. Refojo, D. Wölfel, B. Stalla, J. Vargas, V. Theodoropoulou, M. Buchfelder, M. Paez-Pereda, M. Arzt, E. Stalla, G.K. |
| author_sort |
Labeur, M. |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| url |
http://hdl.handle.net/20.500.12110/paper_00220795_v199_n2_p177_Labeur |
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