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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0011v1 199/2/177    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Labeur, M. Articles by Stalla, G. Search for Related Content PubMed PubMed Citation Articles by Labeur, M. Articles by Stalla, G.

M Labeur, Neuroendocrinology, Max Planck Institute of Psychiatry, 80804, Germany
D Refojo, Molecular Neurogenetics, Max Planck Institute of Psychiatry, 80804, Germany
B Woelfel, Neuroendocrinology, Max Planck Institute of Psychiatry, 80804, Germany
J Stalla, 80804, Germany
V Vargas-Leal, Inflammatory disorders of the CNS, Max Planck Institute of Psychiatry, 80804, Germany
M Theodoropoulou, 80804, Germany
M Buchfelder, Neurosurgery, University of Erlangen, 80804, Germany
M Paez-Pereda, Affectis Pharmaceuticals, 80804, Germany
E Arzt, Fisiologia y Biologia Molecular, University of Buenos Aires, C1428EHA, Argentina
G Stalla, 80804, Germany

Correspondence: Marta Labeur, Email: labeur{at}mpipsykl.mpg.de

Abstract

Interferon- (IFN-) is a cytokine that exerts potent antiproliferative and tumoricidal effects in a variety of cancers. Moreover, IFN- modulates normal pituitary hormone secretion, and was shown to inhibit the expression of the corticotrophin (ACTH) precursor pro-opiomelanocortin (POMC) in murine ACTH secreting AtT-20 tumor cells. We have studied the functional role of IFN- on pituitary tumor cells, focusing in the involvement of IFN- in the molecular events leading to the control of POMC transcriptional repression. Herein it is shown that IFN- inhibits AtT-20 tumor cell proliferation without inducing apoptosis. Unexpectedly, an activated JAK-STAT1 cascade is required for IFN- inhibitory action on POMC promoter activity. NF-B is necessary for the inhibitory action of IFN-on POMC transcription, since loss of NF-B activity with IB super-repressor abolishes this effect. In addition, and β IFN- receptor subunits immunoreactivity was detected in human corticotrophinoma cells. Interestingly, IFN- 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-B-dependent pathway.

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