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

The Journal of Endocrinology
Marta LabeurGünter K Stalla

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-2010/21/2008 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-kappaB) is necessary for the inhibitory action of IFNG on Pomc transcription, since loss of NF-kappaB activity with IkappaB 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...Continue Reading

Citations

Mar 26, 2011·Expert Opinion on Pharmacotherapy·Annamaria ColaoGaetano Lombardi
Dec 12, 2018·The Journal of Clinical Endocrinology and Metabolism·Marily Theodoropoulou, Martin Reincke
May 20, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Tingting ZhuYubin Zhang
Apr 6, 2011·Journal of Endocrinological Investigation·F Pecori GiraldiF Cavagnini
Sep 12, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ran LiTing Lei
Jun 20, 2020·Frontiers in Neuroendocrinology·Pedro MarquesMárta Korbonits
Dec 6, 2018·Neuroimmunomodulation·Ana Clara LibermanClaudio A Serfaty

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