In:
Journal of Cellular Biochemistry, Wiley, Vol. 110, No. 3 ( 2010-06), p. 732-742
Abstract:
Two types of VEGFR‐1 receptors have been characterized: a full‐length transmembrane receptor and a truncated extracellular soluble isoform (sVEGFR‐1). We report here the characterization, in normal and cancer cells, of a new family of intracellular isoforms of VEGFR‐1 resulting from alternative initiation of transcription in intronic sequences of the gene. While the classical isoforms of VEGFR‐1 were barely detectable in MDA‐MB‐231 breast cancer cells, one of the intracellular isoforms transcribed from intron 21 (i 21 VEGFR‐1) was the main isoform expressed in these cells. The new transcript encodes for a protein that contains only the phosphotransferase domain and the carboxyterminal tail of VEGFR‐1. Treatment of MDA‐MB‐231 cells with siRNA specific for the tyrosine domain of VEGFR‐1 suppressed the expression of i 21 VEGFR‐1, downregulated phosphorylation of Src at tyrosine 418, and reduced markedly the invasion capacity of these cells in vitro. Accordingly, overexpression of transfected i 21 VEGFR‐1 in MDA‐MB‐231 cells upregulated the active form of Src and increased invasiveness of MDA‐MB‐231 cells. The expression of i 21 VEGFR‐1 in MDA‐MB‐231 cells was inhibited by retinoic acid. Both, activation of Src and downregulation by retinoic acid, have been reported in other intracellular members of the Fms/Kit/PDGFR family of tyrosine kinases, particularly in the intracellular isoform of c‐kit, analogous structurally to i 21 VEGFR‐1 and frequently expressed in cancer cells. J. Cell. Biochem. 110: 732–742, 2010. © 2010 Wiley‐Liss, Inc.
Type of Medium:
Online Resource
ISSN:
0730-2312
,
1097-4644
Language:
English
Publisher:
Wiley
Publication Date:
2010
detail.hit.zdb_id:
1479976-5
SSG:
12
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