This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Abdelrahim, M. Articles by Safe, S. Search for Related Content PubMed PubMed Citation Articles by Abdelrahim, M. Articles by Safe, S.

Regulation of Vascular Endothelial Growth Factor Receptor-1 Expression by Specificity Proteins 1, 3, and 4 in Pancreatic Cancer Cells

¹ Institute of Biosciences and Technology, Texas A&M University Health Science Center; ² Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center; ³ Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas; ⁴ Cancer Research Institute, M. D. Anderson Cancer Center, Orlando, Florida; and ⁵ Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas

Requests for reprints: Stephen Safe, Department of Veterinary Physiology and Pharmacology, Texas A&M University, 4466 TAMU, Veterinary Research Building 410, College Station, TX 77843-4466. Phone: 979-845-5988; Fax: 979-862-4929; E-mail: ssafe{at}cvm.tamu.edu.

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. [Cancer Res 2007;67(7):3286–94]

This article has been cited by other articles:

				N. Y. Jiang, B. A. Woda, B. F. Banner, G. F. Whalen, K. A. Dresser, and D. Lu Sp1, a New Biomarker That Identifies a Subset of Aggressive Pancreatic Ductal Adenocarcinoma Cancer Epidemiol. Biomarkers Prev., July 1, 2008; 17(7): 1648 - 1652. [Abstract] [Full Text] [PDF]

				G. Chadalapaka, I. Jutooru, S. Chintharlapalli, S. Papineni, R. Smith III, X. Li, and S. Safe Curcumin Decreases Specificity Protein Expression in Bladder Cancer Cells Cancer Res., July 1, 2008; 68(13): 5345 - 5354. [Abstract] [Full Text] [PDF]

				S. U. Mertens-Talcott, S. Chintharlapalli, X. Li, and S. Safe The Oncogenic microRNA-27a Targets Genes That Regulate Specificity Protein Transcription Factors and the G2-M Checkpoint in MDA-MB-231 Breast Cancer Cells Cancer Res., November 15, 2007; 67(22): 11001 - 11011. [Abstract] [Full Text] [PDF]