文档介绍：THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 277, No. 13, Issue of March 29, pp. 11368–11374, 2002
© 2002 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in .
Acidic Extracellular pH Induces Vascular Endothelial Growth
Factor (VEGF) in Human Glioblastoma Cells via ERK1/2 MAPK
Signaling Pathway
MECHANISM OF LOW pH-INDUCED VEGF*
Received for publication, August 29, 2001, and in revised form, November 6, 2001
Published, JBC Papers in Press, December 11, 2001, DOI
Lei Xu, Dai Fukumura, and Rakesh K. Jain‡
From the Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital,
and Harvard Medical School, Boston, Massachusetts 02114
Overexpression of vascular endothelial growth factor glioblastoma multiforme and positively correlates with tumor
(VEGF) is associated with disease progression in human grade in gliomas (4, 5). The critical role of VEGF in tumor
glioblastomas. We recently showed that VEGF promoter growth has been suggested by the targeted deletion of the Downloaded from
activity is inversely correlated with tumor extracellular VEGF gene (6, 7), by blocking antibodies (8) and by introduc-
pH (pHo) in vivo in the human glioma (U87 MG) xe- tion of antisense VEGF constructs into neoplastic cells (9).
nografts. Here we show that substitution of the neutral Hypoxia and gluc