Transformation of vascular endothelial cells by a point mutation in the Tie2 gene from human intramuscular haemangioma.
Tie2, an endothelial-cell-specific receptor tyrosine kinase, collaborates with vascular endothelial growth factor (VEGF) in regulating angiogenesis and vascular maturation. Here, we report a mutation of glycine to aspartic acid at the second glycine of the GXGXXG motif of Tie2 (G833DTie2) in human intramuscular haemangiomas (IMHs) of the capillary type. Murine endothelial cells (ECs) overexpressing this G833DTie2 receptor exhibited an increase in cell proliferation at low serum concentrations and angiosarcomas developed in nude mice, whereas cells overexpressing either wild-type Tie2 or Q837HTie2 failed to elicit these responses. Furthermore, the G833DTie2 receptor increased VEGF expression in ECs. These findings provide molecular mechanisms for pathogenesis of IMH
Wang
Hua
H
Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
Zhang
Yan
Y
Toratani
Shigeaki
S
Okamoto
Tetsuji
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D018076:DNA, Complementary / Q000235:genetics; D042783:Endothelial Cells / Q000473:pathology*; D006391:Hemangioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D042787:Receptor, TIE-2 / Q000737:chemistry / Q000235:genetics*
D018076:DNA, Complementary; D042787:Receptor, TIE-2