PMID- 19934343
OWN - NLM
STAT- MEDLINE
DCOM- 20100216
LR  - 20220311
IS  - 1940-6215 (Electronic)
IS  - 1940-6207 (Print)
IS  - 1940-6215 (Linking)
VI  - 2
IP  - 12
DP  - 2009 Dec
TI  - The cyclooxygenase inhibitor sulindac sulfide inhibits EP4 expression and 
      suppresses the growth of glioblastoma cells.
PG  - 1088-99
LID - 10.1158/1940-6207.CAPR-09-0140 [doi]
AB  - EP4 expression in human glioblastoma cells correlates with growth on soft agar. 
      The cyclooxygenase inhibitor sulindac sulfide first altered specificity protein-1 
      (Sp-1) and early growth response gene-1 expression, then increased the expression 
      of nonsteroidal anti-inflammatory drug-activated gene 1 and activating 
      transcription factor 3, and then decreased EP4 expression. EP4 suppression was 
      dependent on blocking the Sp-1 binding sites in the human EP4 promoter. Mutation 
      in the Sp-1 sites in EP4 altered the promoter activity and abolished sulindac 
      sulfide effects. The inhibitory effect of sulindac sulfide on EP4 expression was 
      reversed by PD98059, a mitogen-activated protein/extracellular signal-regulated 
      kinase kinase-1/extracellular signal-regulated kinase inhibitor. Sp-1 
      phosphorylation was dependent on sulindac sulfide-induced Erk activation. 
      Chromatin immunoprecipitation assay confirmed that Sp-1 phosphorylation decreases 
      Sp-1 binding to DNA and leads to the suppression of EP4. Inhibition of cell 
      growth on soft agar assay was found to be a highly complex process and seems to 
      require not only the inhibition of cyclooxygenase activity but also increased 
      expression of nonsteroidal anti-inflammatory drug-activated gene 1 and activating 
      transcription factor 3 and suppression of EP4 expression. Our data suggest that 
      the suppression of EP4 expression by sulindac sulfide represents a new mechanism 
      for understanding the tumor suppressor activity.
FAU - Kambe, Atsushi
AU  - Kambe A
AD  - Laboratory of Molecular Carcinogenesis, National Institute of Environmental 
      Health Sciences, NIH, Research Triangle Park, NC 27709, USA.
FAU - Yoshioka, Hiroki
AU  - Yoshioka H
FAU - Kamitani, Hideki
AU  - Kamitani H
FAU - Watanabe, Takashi
AU  - Watanabe T
FAU - Baek, Seung Joon
AU  - Baek SJ
FAU - Eling, Thomas E
AU  - Eling TE
LA  - eng
GR  - Z01 ES010016-09/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20091124
PL  - United States
TA  - Cancer Prev Res (Phila)
JT  - Cancer prevention research (Philadelphia, Pa.)
JID - 101479409
RN  - 0 (Activating Transcription Factor 3)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Flavonoids)
RN  - 0 (NBAS protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (PTGER4 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Prostaglandin E)
RN  - 0 (Receptors, Prostaglandin E, EP4 Subtype)
RN  - 0 (Sp1 Transcription Factor)
RN  - 184SNS8VUH (Sulindac)
RN  - 6UVA8S2DEY (sulindac sulfide)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Activating Transcription Factor 3/metabolism
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Blotting, Western
MH  - Brain Neoplasms/*pathology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors
MH  - Chromatin Immunoprecipitation
MH  - Colony-Forming Units Assay
MH  - Cyclooxygenase Inhibitors/*pharmacology
MH  - Early Growth Response Protein 1/metabolism
MH  - Flavonoids/pharmacology
MH  - Glioblastoma/*pathology
MH  - Humans
MH  - Immunoprecipitation
MH  - Luciferases/metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/metabolism
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Neoplasm Proteins/metabolism
MH  - Phosphorylation
MH  - Promoter Regions, Genetic/genetics
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Small Interfering/pharmacology
MH  - Receptors, Prostaglandin E/*antagonists & inhibitors/genetics/metabolism
MH  - Receptors, Prostaglandin E, EP4 Subtype
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sp1 Transcription Factor/metabolism
MH  - Sulindac/*analogs & derivatives/pharmacology
MH  - Tumor Cells, Cultured
PMC - PMC2789193
MID - NIHMS145202
EDAT- 2009/11/26 06:00
MHDA- 2010/02/17 06:00
PMCR- 2010/12/01
CRDT- 2009/11/26 06:00
PHST- 2009/11/26 06:00 [entrez]
PHST- 2009/11/26 06:00 [pubmed]
PHST- 2010/02/17 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - 1940-6207.CAPR-09-0140 [pii]
AID - 10.1158/1940-6207.CAPR-09-0140 [doi]
PST - ppublish
SO  - Cancer Prev Res (Phila). 2009 Dec;2(12):1088-99. doi: 
      10.1158/1940-6207.CAPR-09-0140. Epub 2009 Nov 24.