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Published in: Acta Neuropathologica 3/2006

01-03-2006 | Original Paper

Abundant hypermethylation of SOCS-1 in clinically silent pituitary adenomas

Authors: Rolf Buslei, Jürgen Kreutzer, Bernd Hofmann, Verena Schmidt, Florian Siebzehnrübl, Eric Hahnen, Ilker Y. Eyupoglu, Rudolf Fahlbusch, Ingmar Blümcke

Published in: Acta Neuropathologica | Issue 3/2006

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Abstract

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.
Literature
1.
go back to reference Arzt E, Buric R, Stelzer G, Stalla J, Sauer J, Renner U, Stalla GK (1993) Interleukin involvement in anterior pituitary cell growth regulation: effects of IL-2 and IL-6. Endocrinology 132:459–467CrossRefPubMed Arzt E, Buric R, Stelzer G, Stalla J, Sauer J, Renner U, Stalla GK (1993) Interleukin involvement in anterior pituitary cell growth regulation: effects of IL-2 and IL-6. Endocrinology 132:459–467CrossRefPubMed
2.
go back to reference Auernhammer CJ, Bousquet C, Chesnokova V, Melmed S (2000) SOCS proteins: modulators of neuroimmunoendocrine functions. Impact on corticotroph LIF signaling. Ann N Y Acad Sci 917:658–664PubMedCrossRef Auernhammer CJ, Bousquet C, Chesnokova V, Melmed S (2000) SOCS proteins: modulators of neuroimmunoendocrine functions. Impact on corticotroph LIF signaling. Ann N Y Acad Sci 917:658–664PubMedCrossRef
3.
go back to reference Auernhammer CJ, Melmed S (2001) The central role of SOCS-3 in integrating the neuro-immunoendocrine interface. J Clin Invest 108:1735–1740CrossRefPubMed Auernhammer CJ, Melmed S (2001) The central role of SOCS-3 in integrating the neuro-immunoendocrine interface. J Clin Invest 108:1735–1740CrossRefPubMed
4.
go back to reference Bahar A, Bicknell JE, Simpson DJ, Clayton RN, Farrell WE (2004) Loss of expression of the growth inhibitory gene GADD45gamma, in human pituitary adenomas, is associated with CpG island methylation. Oncogene 23:936–944CrossRefPubMed Bahar A, Bicknell JE, Simpson DJ, Clayton RN, Farrell WE (2004) Loss of expression of the growth inhibitory gene GADD45gamma, in human pituitary adenomas, is associated with CpG island methylation. Oncogene 23:936–944CrossRefPubMed
5.
go back to reference Blaskovich MA, Sun J, Cantor A, Turkson J, Jove R, Sebti SM (2003) Discovery of JSI-124 (cucurbitacin I), a selective Janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice. Cancer Res 63:1270–1279PubMed Blaskovich MA, Sun J, Cantor A, Turkson J, Jove R, Sebti SM (2003) Discovery of JSI-124 (cucurbitacin I), a selective Janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice. Cancer Res 63:1270–1279PubMed
6.
go back to reference Boudny V, Kovarik J (2002) JAK/STAT signaling pathways and cancer. Janus kinases/signal transducers and activators of transcription. Neoplasma 49:349–355PubMed Boudny V, Kovarik J (2002) JAK/STAT signaling pathways and cancer. Janus kinases/signal transducers and activators of transcription. Neoplasma 49:349–355PubMed
7.
go back to reference Buettner R, Mora LB, Jove R (2002) Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res 8:945–954PubMed Buettner R, Mora LB, Jove R (2002) Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res 8:945–954PubMed
8.
go back to reference Buslei R, Nolde M, Hofmann B, Meissner S, Eyupoglu IY, Siebzehnrubl F, Hahnen E, Kreutzer J, Fahlbusch R (2005) Common mutations of beta-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region. Acta Neuropathol (Berl) 109:589–597CrossRef Buslei R, Nolde M, Hofmann B, Meissner S, Eyupoglu IY, Siebzehnrubl F, Hahnen E, Kreutzer J, Fahlbusch R (2005) Common mutations of beta-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region. Acta Neuropathol (Berl) 109:589–597CrossRef
9.
go back to reference Chesnokova V, Melmed S (2002) Minireview: neuro-immuno-endocrine modulation of the hypothalamic-pituitary-adrenal (HPA) axis by gp130 signaling molecules. Endocrinology 143:1571–1574CrossRefPubMed Chesnokova V, Melmed S (2002) Minireview: neuro-immuno-endocrine modulation of the hypothalamic-pituitary-adrenal (HPA) axis by gp130 signaling molecules. Endocrinology 143:1571–1574CrossRefPubMed
10.
go back to reference Cooney RN (2002) Suppressors of cytokine signaling (SOCS): inhibitors of the JAK/STAT pathway. Shock 17:83–90CrossRefPubMed Cooney RN (2002) Suppressors of cytokine signaling (SOCS): inhibitors of the JAK/STAT pathway. Shock 17:83–90CrossRefPubMed
11.
go back to reference Dahia PL, Aguiar RC, Honegger J, Fahlbush R, Jordan S, Lowe DG, Lu X, Clayton RN, Besser GM, Grossman AB (1998) Mutation and expression analysis of the p27/kip1 gene in corticotrophin-secreting tumours. Oncogene 16:69–76CrossRefPubMed Dahia PL, Aguiar RC, Honegger J, Fahlbush R, Jordan S, Lowe DG, Lu X, Clayton RN, Besser GM, Grossman AB (1998) Mutation and expression analysis of the p27/kip1 gene in corticotrophin-secreting tumours. Oncogene 16:69–76CrossRefPubMed
12.
go back to reference Dobrovic A, Bianco T, Tan LW, Sanders T, Hussey D (2002) Screening for and analysis of methylation differences using methylation-sensitive single-strand conformation analysis. Methods 27:134–138CrossRefPubMed Dobrovic A, Bianco T, Tan LW, Sanders T, Hussey D (2002) Screening for and analysis of methylation differences using methylation-sensitive single-strand conformation analysis. Methods 27:134–138CrossRefPubMed
13.
go back to reference Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A (1997) A new protein containing an SH2 domain that inhibits JAK kinases. Nature 387:921–924CrossRefPubMed Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A (1997) A new protein containing an SH2 domain that inhibits JAK kinases. Nature 387:921–924CrossRefPubMed
14.
go back to reference Fahlbusch R, Honegger J, Paulus W, Huk W, Buchfelder M (1999) Surgical treatment of craniopharyngiomas: experience with 168 patients. J Neurosurg 90:237–250PubMedCrossRef Fahlbusch R, Honegger J, Paulus W, Huk W, Buchfelder M (1999) Surgical treatment of craniopharyngiomas: experience with 168 patients. J Neurosurg 90:237–250PubMedCrossRef
15.
go back to reference Farrell WE, Clayton RN (2003) Epigenetic change in pituitary tumorigenesis. Endocr Relat Cancer 10:323–330CrossRefPubMed Farrell WE, Clayton RN (2003) Epigenetic change in pituitary tumorigenesis. Endocr Relat Cancer 10:323–330CrossRefPubMed
16.
go back to reference Fujimoto M, Naka T (2003) Regulation of cytokine signaling by SOCS family molecules. Trends Immunol 24:659–666CrossRefPubMed Fujimoto M, Naka T (2003) Regulation of cytokine signaling by SOCS family molecules. Trends Immunol 24:659–666CrossRefPubMed
17.
18.
go back to reference Galm O, Yoshikawa H, Esteller M, Osieka R, Herman JG (2003) SOCS-1, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma. Blood 101:2784–2788CrossRefPubMed Galm O, Yoshikawa H, Esteller M, Osieka R, Herman JG (2003) SOCS-1, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma. Blood 101:2784–2788CrossRefPubMed
19.
go back to reference Greenhalgh CJ, Rico-Bautista E, Lorentzon M, Thaus AL, Morgan PO, Willson TA, Zervoudakis P, Metcalf D, Street I, Nicola NA, Nash AD, Fabri LJ, Norstedt G, Ohlsson C, Flores-Morales A, Alexander WS, Hilton DJ (2005) SOCS2 negatively regulates growth hormone action in vitro and in vivo. J Clin Invest 115:397–406CrossRefPubMed Greenhalgh CJ, Rico-Bautista E, Lorentzon M, Thaus AL, Morgan PO, Willson TA, Zervoudakis P, Metcalf D, Street I, Nicola NA, Nash AD, Fabri LJ, Norstedt G, Ohlsson C, Flores-Morales A, Alexander WS, Hilton DJ (2005) SOCS2 negatively regulates growth hormone action in vitro and in vivo. J Clin Invest 115:397–406CrossRefPubMed
20.
go back to reference Herman V, Drazin NZ, Gonsky R, Melmed S (1993) Molecular screening of pituitary adenomas for gene mutations and rearrangements. J Clin Endocrinol Metab 77:50–55CrossRefPubMed Herman V, Drazin NZ, Gonsky R, Melmed S (1993) Molecular screening of pituitary adenomas for gene mutations and rearrangements. J Clin Endocrinol Metab 77:50–55CrossRefPubMed
22.
go back to reference Ihle JN (1996) Janus kinases in cytokine signalling. Philos Trans R Soc Lond B Biol Sci 351:159–166PubMedCrossRef Ihle JN (1996) Janus kinases in cytokine signalling. Philos Trans R Soc Lond B Biol Sci 351:159–166PubMedCrossRef
23.
go back to reference Kanda N, Seno H, Konda Y, Marusawa H, Kanai M, Nakajima T, Kawashima T, Nanakin A, Sawabu T, Uenoyama Y, Sekikawa A, Kawada M, Suzuki K, Kayahara T, Fukui H, Sawada M, Chiba T (2004) STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene 23:4921–4929CrossRefPubMed Kanda N, Seno H, Konda Y, Marusawa H, Kanai M, Nakajima T, Kawashima T, Nanakin A, Sawabu T, Uenoyama Y, Sekikawa A, Kawada M, Suzuki K, Kayahara T, Fukui H, Sawada M, Chiba T (2004) STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene 23:4921–4929CrossRefPubMed
24.
go back to reference Karga HJ, Alexander JM, Hedley-Whyte ET, Klibanski A, Jameson JL (1992) Ras mutations in human pituitary tumors. J Clin Endocrinol Metab 74:914–919CrossRefPubMed Karga HJ, Alexander JM, Hedley-Whyte ET, Klibanski A, Jameson JL (1992) Ras mutations in human pituitary tumors. J Clin Endocrinol Metab 74:914–919CrossRefPubMed
25.
go back to reference Kramer JA, Adams MD, Singh GB, Doggett NA, Krawetz SA (1998) Extended analysis of the region encompassing the PRM1–>PRM2–>TNP2 domain: genomic organization, evolution and gene identification. J Exp Zool 282:245–253CrossRefPubMed Kramer JA, Adams MD, Singh GB, Doggett NA, Krawetz SA (1998) Extended analysis of the region encompassing the PRM1–>PRM2–>TNP2 domain: genomic organization, evolution and gene identification. J Exp Zool 282:245–253CrossRefPubMed
26.
go back to reference Krebs DL, Hilton DJ (2000) SOCS: physiological suppressors of cytokine signaling. J Cell Sci 113(16):2813–2819PubMed Krebs DL, Hilton DJ (2000) SOCS: physiological suppressors of cytokine signaling. J Cell Sci 113(16):2813–2819PubMed
27.
go back to reference Liu KD, Gaffen SL, Goldsmith MA (1998) JAK/STAT signaling by cytokine receptors. Curr Opin Immunol 10:271–278CrossRefPubMed Liu KD, Gaffen SL, Goldsmith MA (1998) JAK/STAT signaling by cytokine receptors. Curr Opin Immunol 10:271–278CrossRefPubMed
28.
go back to reference McCabe CJ, Gittoes NJ (1999) PTTG–a new pituitary tumour transforming gene. J Endocrinol 162:163–166CrossRefPubMed McCabe CJ, Gittoes NJ (1999) PTTG–a new pituitary tumour transforming gene. J Endocrinol 162:163–166CrossRefPubMed
29.
go back to reference Mora LB, Buettner R, Seigne J, Diaz J, Ahmad N, Garcia R, Bowman T, Falcone R, Fairclough R, Cantor A, Muro-Cacho C, Livingston S, Karras J, Pow-Sang J, Jove R (2002) Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells. Cancer Res 62:6659–6666PubMed Mora LB, Buettner R, Seigne J, Diaz J, Ahmad N, Garcia R, Bowman T, Falcone R, Fairclough R, Cantor A, Muro-Cacho C, Livingston S, Karras J, Pow-Sang J, Jove R (2002) Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells. Cancer Res 62:6659–6666PubMed
30.
go back to reference Nagai H, Naka T, Terada Y, Komazaki T, Yabe A, Jin E, Kawanami O, Kishimoto T, Konishi N, Nakamura M, Kobayashi Y, Emi M (2003) Hypermethylation associated with inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human hepatoblastomas. J Hum Genet 48:65–69CrossRefPubMed Nagai H, Naka T, Terada Y, Komazaki T, Yabe A, Jin E, Kawanami O, Kishimoto T, Konishi N, Nakamura M, Kobayashi Y, Emi M (2003) Hypermethylation associated with inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human hepatoblastomas. J Hum Genet 48:65–69CrossRefPubMed
31.
go back to reference Naka T, Narazaki M, Hirata M, Matsumoto T, Minamoto S, Aono A, Nishimoto N, Kajita T, Taga T, Yoshizaki K, Akira S, Kishimoto T (1997) Structure and function of a new STAT-induced STAT inhibitor. Nature 387:924–929CrossRefPubMed Naka T, Narazaki M, Hirata M, Matsumoto T, Minamoto S, Aono A, Nishimoto N, Kajita T, Taga T, Yoshizaki K, Akira S, Kishimoto T (1997) Structure and function of a new STAT-induced STAT inhibitor. Nature 387:924–929CrossRefPubMed
32.
go back to reference Newell-Price J, King P, Clark AJ (2001) The CpG island promoter of the human proopiomelanocortin gene is methylated in nonexpressing normal tissue and tumors and represses expression. Mol Endocrinol 15:338–348CrossRefPubMed Newell-Price J, King P, Clark AJ (2001) The CpG island promoter of the human proopiomelanocortin gene is methylated in nonexpressing normal tissue and tumors and represses expression. Mol Endocrinol 15:338–348CrossRefPubMed
33.
go back to reference Okochi O, Hibi K, Sakai M, Inoue S, Takeda S, Kaneko T, Nakao A (2003) Methylation-mediated silencing of SOCS-1 gene in hepatocellular carcinoma derived from cirrhosis. Clin Cancer Res 9:5295–5298PubMed Okochi O, Hibi K, Sakai M, Inoue S, Takeda S, Kaneko T, Nakao A (2003) Methylation-mediated silencing of SOCS-1 gene in hepatocellular carcinoma derived from cirrhosis. Clin Cancer Res 9:5295–5298PubMed
34.
go back to reference Oshimo Y, Kuraoka K, Nakayama H, Kitadai Y, Yoshida K, Chayama K, Yasui W (2004) Epigenetic inactivation of SOCS-1 by CpG island hypermethylation in human gastric carcinoma. Int J Cancer 112:1003–1009CrossRefPubMed Oshimo Y, Kuraoka K, Nakayama H, Kitadai Y, Yoshida K, Chayama K, Yasui W (2004) Epigenetic inactivation of SOCS-1 by CpG island hypermethylation in human gastric carcinoma. Int J Cancer 112:1003–1009CrossRefPubMed
35.
go back to reference Qian ZR, Sano T, Yoshimoto K, Yamada S, Ishizuka A, Mizusawa N, Horiguchi H, Hirokawa M, Asa SL (2005) Inactivation of RASSF1A tumor suppressor gene by aberrant promoter hypermethylation in human pituitary adenomas. Lab Invest 85:464–473CrossRefPubMed Qian ZR, Sano T, Yoshimoto K, Yamada S, Ishizuka A, Mizusawa N, Horiguchi H, Hirokawa M, Asa SL (2005) Inactivation of RASSF1A tumor suppressor gene by aberrant promoter hypermethylation in human pituitary adenomas. Lab Invest 85:464–473CrossRefPubMed
36.
go back to reference Quan N, Herkenham M (2002) Connecting cytokines and brain: a review of current issues. Histol Histopathol 17:273–288PubMed Quan N, Herkenham M (2002) Connecting cytokines and brain: a review of current issues. Histol Histopathol 17:273–288PubMed
37.
go back to reference Rottapel R, Ilangumaran S, Neale C, La Rose J, Ho JM, Nguyen MH, Barber D, Dubreuil P, de Sepulveda P (2002) The tumor suppressor activity of SOCS-1. Oncogene 21:4351–4362CrossRefPubMed Rottapel R, Ilangumaran S, Neale C, La Rose J, Ho JM, Nguyen MH, Barber D, Dubreuil P, de Sepulveda P (2002) The tumor suppressor activity of SOCS-1. Oncogene 21:4351–4362CrossRefPubMed
38.
go back to reference Ruebel KH, Jin L, Qian X, Scheithauer BW, Kovacs K, Nakamura N, Zhang H, Raz A, Lloyd RV (2005) Effects of DNA methylation on galectin-3 expression in pituitary tumors. Cancer Res 65:1136–1140CrossRefPubMed Ruebel KH, Jin L, Qian X, Scheithauer BW, Kovacs K, Nakamura N, Zhang H, Raz A, Lloyd RV (2005) Effects of DNA methylation on galectin-3 expression in pituitary tumors. Cancer Res 65:1136–1140CrossRefPubMed
39.
go back to reference Sano T, Rong QZ, Kagawa N, Yamada S (2004) Down-regulation of E-cadherin and catenins in human pituitary growth hormone-producing adenomas. Front Horm Res 32:127–132PubMed Sano T, Rong QZ, Kagawa N, Yamada S (2004) Down-regulation of E-cadherin and catenins in human pituitary growth hormone-producing adenomas. Front Horm Res 32:127–132PubMed
40.
go back to reference Sekine S, Shibata T, Kokubu A, Morishita Y, Noguchi M, Nakanishi Y, Sakamoto M, Hirohashi S (2002) Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations. Am J Pathol 161:1997–2001PubMed Sekine S, Shibata T, Kokubu A, Morishita Y, Noguchi M, Nakanishi Y, Sakamoto M, Hirohashi S (2002) Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations. Am J Pathol 161:1997–2001PubMed
41.
go back to reference Sekine S, Takata T, Shibata T, Mori M, Morishita Y, Noguchi M, Uchida T, Kanai Y, Hirohashi S (2004) Expression of enamel proteins and LEF1 in adamantinomatous craniopharyngioma: evidence for its odontogenic epithelial differentiation. Histopathology 45:573–579CrossRefPubMed Sekine S, Takata T, Shibata T, Mori M, Morishita Y, Noguchi M, Uchida T, Kanai Y, Hirohashi S (2004) Expression of enamel proteins and LEF1 in adamantinomatous craniopharyngioma: evidence for its odontogenic epithelial differentiation. Histopathology 45:573–579CrossRefPubMed
42.
go back to reference Shimon I, Yan X, Ray DW, Melmed S (1997) Cytokine-dependent gp130 receptor subunit regulates human fetal pituitary adrenocorticotropin hormone and growth hormone secretion. J Clin Invest 100:357–363PubMed Shimon I, Yan X, Ray DW, Melmed S (1997) Cytokine-dependent gp130 receptor subunit regulates human fetal pituitary adrenocorticotropin hormone and growth hormone secretion. J Clin Invest 100:357–363PubMed
43.
go back to reference Simpson DJ, Bicknell JE, McNicol AM, Clayton RN, Farrell WE (1999) Hypermethylation of the p16/CDKN2A/MTSI gene and loss of protein expression is associated with nonfunctional pituitary adenomas but not somatotrophinomas. Genes Chromosomes Cancer 24:328–336CrossRefPubMed Simpson DJ, Bicknell JE, McNicol AM, Clayton RN, Farrell WE (1999) Hypermethylation of the p16/CDKN2A/MTSI gene and loss of protein expression is associated with nonfunctional pituitary adenomas but not somatotrophinomas. Genes Chromosomes Cancer 24:328–336CrossRefPubMed
44.
go back to reference Simpson DJ, Hibberts NA, McNicol AM, Clayton RN, Farrell WE (2000) Loss of pRb expression in pituitary adenomas is associated with methylation of the RB1 CpG island. Cancer Res 60:1211–1216PubMed Simpson DJ, Hibberts NA, McNicol AM, Clayton RN, Farrell WE (2000) Loss of pRb expression in pituitary adenomas is associated with methylation of the RB1 CpG island. Cancer Res 60:1211–1216PubMed
45.
go back to reference Starr R, Hilton DJ (1998) SOCS: suppressors of cytokine signalling. Int J Biochem Cell Biol 30:1081–1085CrossRefPubMed Starr R, Hilton DJ (1998) SOCS: suppressors of cytokine signalling. Int J Biochem Cell Biol 30:1081–1085CrossRefPubMed
46.
go back to reference Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, Gonda TJ, Alexander WS, Metcalf D, Nicola NA, Hilton DJ (1997) A family of cytokine-inducible inhibitors of signalling. Nature 387:917–921CrossRefPubMed Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, Gonda TJ, Alexander WS, Metcalf D, Nicola NA, Hilton DJ (1997) A family of cytokine-inducible inhibitors of signalling. Nature 387:917–921CrossRefPubMed
47.
go back to reference Sutherland KD, Lindeman GJ, Choong DY, Wittlin S, Brentzell L, Phillips W, Campbell IG, Visvader JE (2004) Differential hypermethylation of SOCS genes in ovarian and breast carcinomas. Oncogene 23:7726–7733CrossRefPubMed Sutherland KD, Lindeman GJ, Choong DY, Wittlin S, Brentzell L, Phillips W, Campbell IG, Visvader JE (2004) Differential hypermethylation of SOCS genes in ovarian and breast carcinomas. Oncogene 23:7726–7733CrossRefPubMed
48.
go back to reference Thapar K, Kovacs K (1998) Neoplasms of the sellar region. In: Russell and Rubinstein´s Pathology of Tumors of the Nervous System, edn 6, pp 629–680 Thapar K, Kovacs K (1998) Neoplasms of the sellar region. In: Russell and Rubinstein´s Pathology of Tumors of the Nervous System, edn 6, pp 629–680
49.
go back to reference Thiele JO, Lohrer P, Schaaf L, Feirer M, Stummer W, Losa M, Lange M, Tichomirowa M, Arzt E, Stalla GK, Renner U (2003) Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas. Eur J Endocrinol 149:455–461CrossRefPubMed Thiele JO, Lohrer P, Schaaf L, Feirer M, Stummer W, Losa M, Lange M, Tichomirowa M, Arzt E, Stalla GK, Renner U (2003) Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas. Eur J Endocrinol 149:455–461CrossRefPubMed
50.
go back to reference Vallar L, Spada A, Giannattasio G (1987) Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas. Nature 330:566–568CrossRefPubMed Vallar L, Spada A, Giannattasio G (1987) Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas. Nature 330:566–568CrossRefPubMed
51.
go back to reference Wang J, Campbell IL (2002) Cytokine signaling in the brain: putting a SOCS in it? J Neurosci Res 67:423–427CrossRefPubMed Wang J, Campbell IL (2002) Cytokine signaling in the brain: putting a SOCS in it? J Neurosci Res 67:423–427CrossRefPubMed
52.
go back to reference Watanabe D, Ezoe S, Fujimoto M, Kimura A, Saito Y, Nagai H, Tachibana I, Matsumura I, Tanaka T, Kanegane H, Miyawaki T, Emi M, Kanakura Y, Kawase I, Naka T, Kishimoto T (2004) Suppressor of cytokine signalling-1 gene silencing in acute myeloid leukaemia and human haematopoietic cell lines. Br J Haematol 126:726–735CrossRefPubMed Watanabe D, Ezoe S, Fujimoto M, Kimura A, Saito Y, Nagai H, Tachibana I, Matsumura I, Tanaka T, Kanegane H, Miyawaki T, Emi M, Kanakura Y, Kawase I, Naka T, Kishimoto T (2004) Suppressor of cytokine signalling-1 gene silencing in acute myeloid leukaemia and human haematopoietic cell lines. Br J Haematol 126:726–735CrossRefPubMed
53.
go back to reference Watanabe D, Naka T, Kishimoto T (2004) Implication of SOCS-1 gene methylation in acute myeloid leukaemia. Br J Haematol 127:608–609CrossRefPubMed Watanabe D, Naka T, Kishimoto T (2004) Implication of SOCS-1 gene methylation in acute myeloid leukaemia. Br J Haematol 127:608–609CrossRefPubMed
54.
go back to reference Woloschak M, Yu A, Post KD (1997) Frequent inactivation of the p16 gene in human pituitary tumors by gene methylation. Mol Carcinog 19:221–224CrossRefPubMed Woloschak M, Yu A, Post KD (1997) Frequent inactivation of the p16 gene in human pituitary tumors by gene methylation. Mol Carcinog 19:221–224CrossRefPubMed
55.
56.
go back to reference Yamashita H, Iwase H, Toyama T, Fujii Y (2003) Naturally occurring dominant-negative Stat5 suppresses transcriptional activity of estrogen receptors and induces apoptosis in T47D breast cancer cells. Oncogene 22:1638–1652CrossRefPubMed Yamashita H, Iwase H, Toyama T, Fujii Y (2003) Naturally occurring dominant-negative Stat5 suppresses transcriptional activity of estrogen receptors and induces apoptosis in T47D breast cancer cells. Oncogene 22:1638–1652CrossRefPubMed
57.
go back to reference Yoshikawa H, Matsubara K, Qian GS, Jackson P, Groopman JD, Manning JE, Harris CC, Herman JG (2001) SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity. Nat Genet 28:29–35CrossRefPubMed Yoshikawa H, Matsubara K, Qian GS, Jackson P, Groopman JD, Manning JE, Harris CC, Herman JG (2001) SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity. Nat Genet 28:29–35CrossRefPubMed
58.
go back to reference Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD, Melmed S (1999) Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab 84:761–767CrossRefPubMed Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD, Melmed S (1999) Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab 84:761–767CrossRefPubMed
Metadata
Title
Abundant hypermethylation of SOCS-1 in clinically silent pituitary adenomas
Authors
Rolf Buslei
Jürgen Kreutzer
Bernd Hofmann
Verena Schmidt
Florian Siebzehnrübl
Eric Hahnen
Ilker Y. Eyupoglu
Rudolf Fahlbusch
Ingmar Blümcke
Publication date
01-03-2006
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 3/2006
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-005-0009-9

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