title: SOCS2 correlates with malignancy and exerts growth-promoting effects in prostate cancer.
abstract: Deregulation of cytokine and growth factor signaling due to an altered expression of endogenous regulators is well recognized in prostate cancer (PCa) and other cancers. Suppressor of cytokine signaling 2 (SOCS2) is a key regulator of the GH, IGF, and prolactin signaling pathways that have been implicated in carcinogenesis. In this study, we evaluated the expression patterns and functional significance of SOCS2 in PCa. Protein expression analysis employing tissue microarrays from two independent patient cohorts revealed a significantly enhanced expression in tumor tissue compared with benign tissue as well as association with Gleason score and disease progression. In vitro and in vivo assays uncovered the involvement of SOCS2 in the regulation of cell growth and apoptosis. Functionally, SOCS2 knockdown inhibited PCa cell proliferation and xenograft growth in a CAM assay. Decreased cell growth after SOCS2 downregulation was associated with cell-cycle arrest and apoptosis. In addition, we proved that SOCS2 expression is significantly elevated upon androgenic stimulation in androgen receptor (AR)-positive cell lines, providing a possible mechanistic explanation for high SOCS2 levels in PCa tissue. Consequently, SOCS2 expression correlated with AR expression in the malignant tissue of patients. On the whole, our study linked increased SOCS2 expression in PCa with a pro-proliferative role in vitro and in vivo.
authors.affiliation: Experimental Urology, Department of Urology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria Oncotyrol Laboratory for Tumor Biology and Angiogenesis, Innsbruck, Austria Institute of Pathology, University Hospital Bonn, Bonn, Germany Division of Molecular Pathophysiology, Innsbruck Biocenter, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoefer
authors.forename: Johann
authors.initials: J
authors.lastname: Kern
authors.forename: Philipp
authors.initials: P
authors.lastname: Ofer
authors.forename: Iris E
authors.initials: IE
authors.lastname: Eder
authors.forename: Georg
authors.initials: G
authors.lastname: Schäfer
authors.forename: Dimo
authors.initials: D
authors.lastname: Dietrich
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Stephan
authors.initials: S
authors.lastname: Geley
authors.forename: Johannes
authors.initials: J
authors.lastname: Rainer
authors.forename: Eberhard
authors.initials: E
authors.lastname: Gunsilius
authors.forename: Helmut
authors.initials: H
authors.lastname: Klocker
authors.forename: Zoran
authors.initials: Z
authors.lastname: Culig
authors.forename: Martin
authors.initials: M
authors.lastname: Puhr
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D047368:Tumor Burden
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen; C106643:SOCS2 protein, human; D050826:Suppressor of Cytokine Signaling Proteins
keywords: SOCS2; androgen; proliferation; prostate cancer; survival