title: Correlative analyses of the expression levels of PIAS3, p-SHP2, SOCS1 and SOCS3 with STAT3 activation in human astrocytomas.
abstract: The importance of signal transducer and activator of transcription 3 (STAT3) signaling in the growth and survival of glioblastoma cells has been well documented, while the reasons leading to STAT3 activation remains to be elucidated. Suppressors of cytokine signaling (SOCS) 1 and SOCS3, SH2 domain‑containing phosphatase (SHP2) and protein inhibitors of activated STAT3 (PIAS3) are known to inhibit STAT3 signal transduction, while their expression statuses in the four grades of astrocytomas and relevance with STAT3 activation remain to be described. The present study aimed to address these issues by tissue microarray‑based immunohistochemical profiling the expression levels of phosphorylated (p)‑STAT3, SOCS1, SOCS3, PIAS3 and p‑SHP2. The results revealed that p‑STAT3 nuclear translocation was rarely observed in non‑cancerous brain tissues and its frequencies were increased in a tumor grade‑associated manner (65.2, 77.1, 81.8 and 85.7% for grade I‑IV, respectively). PIAS3, p‑SHP2, SOCS1 and SOCS3 were expressed in higher levels (++ and +++) in 63.6, 90, 87.5 and 81.8% of tumor surrounding brain tissues, which reduced to 13.1, 47.8, 33.3 and 50% in grade I, 11.4, 65.7, 58.3 and 77.1% in grade II, 9.1, 63.6, 38.1 and 31.8% in grade III and 7.1, 66.7, 30.8 and 7.1% in grade IV astrocytomas. The above results revealed that although the expression levels of SOCS1, SOCS3 and, in particular, p‑SHP2, tend to decrease in the four types of astrocytomas, PIAS3 downregulation is more negatively correlated with STAT3 activation in the stepwise progress of astrocytomas and would indicate an unfavorable outcome.
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics, Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Liu
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics, Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics, Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Cheng
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics, Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Qing-You
authors.initials: QY
authors.lastname: Kong
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics, Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics, Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Mo-Li
authors.initials: ML
authors.lastname: Wu
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics, Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics, Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics, Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
mesh_terms: D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D018832:Molecular Chaperones / Q000032:analysis* / Q000378:metabolism; D050828:Protein Inhibitors of Activated STAT / Q000032:analysis* / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000032:analysis* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000032:analysis* / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000032:analysis* / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000032:analysis* / Q000378:metabolism
chemical_list: D018832:Molecular Chaperones; C484745:PIAS3 protein, human; D050828:Protein Inhibitors of Activated STAT; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11