Expression of STATs and their inhibitors SOCS and PIAS in brain tumors. In vitro and in vivo study.
Proteins of STAT family belongs to the transcription factors. Through their binding to the DNA specific sites and consequent regulation of transcription of various genes, these signaling proteins play an important role in many cell functions. Recent studies demonstrated persistent activation of STATs and loss of their natural inhibitors SOCS and PIAS in various human cancers. There is also evidence that experimental pharmacologic or genetic modulation of their function mignt by a new approach in anticancer treatment. The aim of this study was in vitro assesment and analysis of expression of STATs, SOCS and PIAS in glioblastoma cell lines undergoing treatment by PPARgamma agonists/antagonists because PPARgamma and STATs are tightly regulated by an overlapping set of nuclear regulatory proteins. We further analysed immunohistochemical expression of these proteins in vivo, with its correlation to grading in various brain tumors. The results of in vitro study showed decreased expression of phosphorylated form of STAT3 and increase of its inhibitors SOCS3 and PIAS3 in glioblastoma cell lines after treatment with IC50 of PPARgamma agonist ciglitazone. In vivo study failed to reveal changes in STAT3 and SOCS3 expression in either low and high grade astrocytomas, however we detect lower expression of STAT2 in low grade astrocytomas when comparing with high grade astrocytomas and lower expression of STAT3 in ependymomas when comparing with anaplastic ones. The results showed existing relationship between STAT and PPARgamma signaling in glial tumors and further suppport expected important role of STATs in regulation of growth and differentiation in these tumors.
Ehrmann
J
J
Laboratory of Molecular Pathology & Department of Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic. jiri.ehrmann@tiscali.cz
Strakova
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Vrzalikova
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Hezova
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Kolar
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Z
D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D015870:Gene Expression; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D015533:Transcriptional Activation
D018832:Molecular Chaperones; C106529:PIAS1 protein, human; C484745:PIAS3 protein, human; D047495:PPAR gamma; D050828:Protein Inhibitors of Activated STAT; C106644:SOCS3 protein, human; D050791:STAT Transcription Factors; D050796:STAT3 Transcription Factor; D025841:Small Ubiquitin-Related Modifier Proteins; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D045162:Thiazolidinediones; C039671:ciglitazone