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Interferon-gamma 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

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons80417

Labeur,  M.
AG Stalla, Günter, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80487

Refojo,  D.
AG Deussing, Jan, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80595

Wölfel,  B.
AG Stalla, Günter, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80540

Stalla,  J.
AG Stalla, Günter, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80566

Vargas,  V.
Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80549

Theodoropoulou,  M.
AG Stalla, Günter, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80467

Paez-Pereda,  M.
AG Stalla, Günter, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80253

Arzt,  E.
Max Planck Institute of Psychiatry, Max Planck Society;

Stalla,  G. K.
Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Labeur, M., Refojo, D., Wölfel, B., Stalla, J., Vargas, V., Theodoropoulou, M., et al. (2008). Interferon-gamma 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.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-939B-4
Abstract
Interferon-gamma (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 POW promoter activity. Factor-kappa B (NF-kappa B) is necessary for the inhibitory action of IFNG on Pomc transcription, since loss of NF-kappa B activity with I kappa B 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-kappa B-depenclent pathway.