PMID- 18676737
OWN - NLM
STAT- MEDLINE
DCOM- 20080908
LR  - 20211020
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 14
IP  - 15
DP  - 2008 Aug 1
TI  - Loss of protein inhibitors of activated STAT-3 expression in glioblastoma 
      multiforme tumors: implications for STAT-3 activation and gene expression.
PG  - 4694-704
LID - 10.1158/1078-0432.CCR-08-0618 [doi]
AB  - PURPOSE: STATs activate transcription in response to numerous cytokines, 
      controlling proliferation, gene expression, and apoptosis. Aberrant activation of 
      STAT proteins, particularly STAT-3, is implicated in the pathogenesis of many 
      cancers, including GBM, by promoting cell cycle progression, stimulating 
      angiogenesis, and impairing tumor immune surveillance. Little is known about the 
      endogenous STAT inhibitors, the PIAS proteins, in human malignancies. The 
      objective of this study was to examine the expression of STAT-3 and its negative 
      regulator, PIAS3, in human tissue samples from control and GBM brains. 
      EXPERIMENTAL DESIGN: Control and GBM human tissues were analyzed by 
      immunoblotting and immunohistochemistry to determine the activation status of 
      STAT-3 and expression of the PIAS3 protein. The functional consequence of PIAS3 
      inhibition by small interfering RNA or PIAS3 overexpression in GBM cells was 
      determined by examining cell proliferation, STAT-3 transcriptional activity, and 
      STAT-3 target gene expression. This was accomplished using [(3)H]TdR 
      incorporation, STAT-3 dominant-negative constructs, reverse transcription-PCR, 
      and immunoblotting. RESULTS AND CONCLUSIONS: STAT-3 activation, as assessed by 
      tyrosine and serine phosphorylation, was elevated in GBM tissue compared with 
      control tissue. Interestingly, we observed expression of PIAS3 in control tissue, 
      whereas PIAS3 protein expression in GBM tissue was greatly reduced. Inhibition of 
      PIAS3 resulted in enhanced glioblastoma cellular proliferation. Conversely, PIAS3 
      overexpression inhibited STAT-3 transcriptional activity, expression of 
      STAT-3-regulated genes, and cell proliferation. We propose that the loss of PIAS3 
      in GBM contributes to enhanced STAT-3 transcriptional activity and subsequent 
      cell proliferation.
FAU - Brantley, Emily C
AU  - Brantley EC
AD  - Department of Cell Biology, University of Alabama at Birmingham, Birmingham, 
      Alabama 35294-0005, USA.
FAU - Nabors, L Burton
AU  - Nabors LB
FAU - Gillespie, G Yancey
AU  - Gillespie GY
FAU - Choi, Youn-Hee
AU  - Choi YH
FAU - Palmer, Cheryl Ann
AU  - Palmer CA
FAU - Harrison, Keith
AU  - Harrison K
FAU - Roarty, Kevin
AU  - Roarty K
FAU - Benveniste, Etty N
AU  - Benveniste EN
LA  - eng
GR  - R01 CA112397/CA/NCI NIH HHS/United States
GR  - R21 NS054158/NS/NINDS NIH HHS/United States
GR  - P50 CA097247/CA/NCI NIH HHS/United States
GR  - CA-112397/CA/NCI NIH HHS/United States
GR  - P50 CA-097247/CA/NCI NIH HHS/United States
GR  - P30 NS047466/NS/NINDS NIH HHS/United States
GR  - NS-54158/NS/NINDS NIH HHS/United States
GR  - R25 CA-47888/CA/NCI NIH HHS/United States
GR  - R25 CA047888/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (RNA, Small Interfering)
RN  - 0 (SOCS3 protein, human)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - 452VLY9402 (Serine)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - *Gene Expression Regulation, Neoplastic
MH  - Glioblastoma/*drug therapy/*metabolism
MH  - Humans
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Phosphorylation
MH  - RNA, Small Interfering/metabolism
MH  - STAT3 Transcription Factor/*metabolism
MH  - Serine/chemistry
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins/metabolism
MH  - Transcription, Genetic
MH  - Transcriptional Activation
MH  - Tyrosine/chemistry
PMC - PMC3886729
MID - NIHMS513583
EDAT- 2008/08/05 09:00
MHDA- 2008/09/09 09:00
PMCR- 2014/01/09
CRDT- 2008/08/05 09:00
PHST- 2008/08/05 09:00 [pubmed]
PHST- 2008/09/09 09:00 [medline]
PHST- 2008/08/05 09:00 [entrez]
PHST- 2014/01/09 00:00 [pmc-release]
AID - 14/15/4694 [pii]
AID - 10.1158/1078-0432.CCR-08-0618 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2008 Aug 1;14(15):4694-704. doi: 10.1158/1078-0432.CCR-08-0618.