PMID- 17409437
OWN - NLM
STAT- MEDLINE
DCOM- 20070509
LR  - 20220311
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 67
IP  - 7
DP  - 2007 Apr 1
TI  - Regulation of vascular endothelial growth factor receptor-1 expression by 
      specificity proteins 1, 3, and 4 in pancreatic cancer cells.
PG  - 3286-94
AB  - Vascular endothelial growth factor receptor-1 (VEGFR1) is expressed in cancer 
      cell lines and tumors and, in pancreatic and colon cancer cells, activation of 
      VEGFR1 is linked to increased tumor migration and invasiveness. Tolfenamic acid, 
      a nonsteroidal anti-inflammatory drug, decreases Sp protein expression in Panc-1 
      and L3.6pl pancreatic cancer cells, and this was accompanied by decreased VEGFR1 
      protein and mRNA and decreased luciferase activity on cells transfected with 
      constructs (pVEGFR1) containing VEGFR1 promoter inserts. Comparable results were 
      obtained in pancreatic cancer cells transfected with small inhibitory RNAs for 
      Sp1, Sp3, and Sp4 and all three proteins bound to GC-rich elements in the VEGFR1 
      promoter. These results show that VEGFR1 is regulated by Sp proteins and that 
      treatment with tolfenamic acid decreases expression of this critical angiogenic 
      factor. Moreover, in vitro studies in Panc-1 cells show that activation of VEGFR1 
      by VEGFB to increase mitogen-activated protein kinase 1/2 phosphorylation and 
      cell migration on collagen-coated plates is also inhibited by tolfenamic acid. 
      Thus, targeted degradation of Sp proteins is highly effective for inhibiting 
      VEGFR1 and associated angiogenic responses in pancreatic cancer.
FAU - Abdelrahim, Maen
AU  - Abdelrahim M
AD  - Institute of Biosciences and Technology, Texas A&M University Health Science 
      Center, Houston, Texas, USA.
FAU - Baker, Cheryl H
AU  - Baker CH
FAU - Abbruzzese, James L
AU  - Abbruzzese JL
FAU - Sheikh-Hamad, David
AU  - Sheikh-Hamad D
FAU - Liu, Shengxi
AU  - Liu S
FAU - Cho, Sung Dae
AU  - Cho SD
FAU - Yoon, Kyungsil
AU  - Yoon K
FAU - Safe, Stephen
AU  - Safe S
LA  - eng
GR  - CA108178/CA/NCI NIH HHS/United States
GR  - ES09106/ES/NIEHS NIH HHS/United States
GR  - P20-CA-10193/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (RNA, Messenger)
RN  - 0 (SP3 protein, human)
RN  - 0 (SP4 protein, human)
RN  - 0 (Sp Transcription Factors)
RN  - 0 (Sp1 Transcription Factor)
RN  - 0 (Sp4 Transcription Factor)
RN  - 0 (VEGFB protein, human)
RN  - 0 (Vascular Endothelial Growth Factor B)
RN  - 0 (ortho-Aminobenzoates)
RN  - 148710-94-5 (Sp3 Transcription Factor)
RN  - 3G943U18KM (tolfenamic acid)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Movement/physiology
MH  - Humans
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Neoplasm Invasiveness
MH  - Pancreatic Neoplasms/blood supply/genetics/*metabolism/pathology
MH  - Phosphorylation
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Sp Transcription Factors/*metabolism
MH  - Sp1 Transcription Factor/metabolism
MH  - Sp3 Transcription Factor/metabolism
MH  - Sp4 Transcription Factor/metabolism
MH  - Transfection
MH  - Vascular Endothelial Growth Factor B/metabolism
MH  - Vascular Endothelial Growth Factor Receptor-1/*biosynthesis/genetics
MH  - ortho-Aminobenzoates/pharmacology
EDAT- 2007/04/06 09:00
MHDA- 2007/05/10 09:00
CRDT- 2007/04/06 09:00
PHST- 2007/04/06 09:00 [pubmed]
PHST- 2007/05/10 09:00 [medline]
PHST- 2007/04/06 09:00 [entrez]
AID - 67/7/3286 [pii]
AID - 10.1158/0008-5472.CAN-06-3831 [doi]
PST - ppublish
SO  - Cancer Res. 2007 Apr 1;67(7):3286-94. doi: 10.1158/0008-5472.CAN-06-3831.