Abundant hypermethylation of SOCS-1 in clinically silent pituitary adenomas

Janus kinase (JAK)/signal transducers and activators of transcription (STAT) cascade are required for cytokines, growth factors, G-proteins and hormones (growth hormone and prolactin). Gatekeepers in this pathway are the suppressor of cytokine signalling (SOCS) family of proteins. Their expression l...

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Bibliographic Details
Published in:Acta neuropathologica 2006-03, Vol.111 (3), p.264-271
Main Authors: Buslei, Rolf, Kreutzer, Jürgen, Hofmann, Bernd, Schmidt, Verena, Siebzehnrübl, Florian, Hahnen, Eric, Eyupoglu, Ilker Y, Fahlbusch, Rudolf, Blümcke, Ingmar
Format: Article
Language:English
Subjects:
Adenoma - genetics
Adenoma - metabolism
Adolescent
Adult
Aged
Autopsies
Cloning
Craniopharyngioma - genetics
Craniopharyngioma - metabolism
Cytokines
DNA Methylation
DNA, Neoplasm - metabolism
Female
Gene Expression Regulation, Neoplastic
Gene Silencing
Growth factors
Growth hormones
Humans
Janus Kinases - physiology
Kinases
Male
Middle Aged
Neuropathology
Neurosurgery
Pituitary gland
Pituitary Neoplasms - genetics
Pituitary Neoplasms - metabolism
Proteins
Signal transduction
Signal Transduction - physiology
STAT Transcription Factors - physiology
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling Proteins - genetics
Suppressor of Cytokine Signaling Proteins - metabolism
Tumors
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Summary:Janus kinase (JAK)/signal transducers and activators of transcription (STAT) cascade are required for cytokines, growth factors, G-proteins and hormones (growth hormone and prolactin). Gatekeepers in this pathway are the suppressor of cytokine signalling (SOCS) family of proteins. Their expression level is epigenetically regulated by DNA methylation. We have investigated the CpG island methylation status of SOCS-1 in a cohort of pituitary adenomas (PA; n=57), craniopharyngiomas (CP; n=30) and normal pituitary tissue (NP; n=11) using methylation sensitive single-strand conformation polymorphism analysis (MS-SSCP) and direct sequencing. SOCS-1 hypermethylation was identified in 51% (29/57) of surgical specimens obtained from PA patients. 83% of these tumours were clinically silent. In contrast, no methylation of SOCS-1 was observed in CPs or NPs. Quantitative real-time PCR and western blot analysis confirmed reduced SOCS-1 expression in the majority of pituitary adenomas. The data is compatible with epigenetic silencing of the SOCS-1 gene and constitutive activation of the JAK-STAT pathway in PA. This appears to contribute particularly to those tumours characterized by a hormone-inactive status.
ISSN:0001-6322
1432-0533
DOI:10.1007/s00401-005-0009-9