title: Disease-specific expression of VEGF and its receptors in AML cells: possible autocrine pathway of VEGF/type1 receptor of VEGF in t(15;17) AML and VEGF/type2 receptor of VEGF in t(8;21) AML.
abstract: Various angiogenic factors, such as vascular endothelial growth factor (VEGF) and an associated molecule, placenta growth factor (PlGF), are thought to be important for normal and malignant hematopoiesis. This study examined mRNA expression of VEGF, PlGF and receptors for these molecules in AML cells and identified the disease-specific patterns of expression. AML M3 having t(15;17) abnormality showed highest expression of VEGF and VEGF receptor type 1 (VEGFR1), suggesting the autocrine pathway of VEGF-VEGFR1. Then, t(8;21) AML demonstrated augmented expression of VEGF and VEGF receptor type 2 (VEGFR2), suggesting VEGF-VEGFR2 autocrine pathway. Then, addition of VEGFR2 kinase inhibitor in Kasumi-1, a t(8;21) AML cell line, resulted in marked inhibition of cell growth, although growth inhibitory effect of R2 kinase inhibitor to HL-60 was marginal. In addition, cell cycle analysis study showed S-phase cell population reduction by R2 kinase inhibitor in Kasumi-1, but not in HL-60. This observation is thought to be the rationale for novel molecular target therapy directed to angiogenic molecules.
authors.affiliation: Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Hiramatsu
authors.forename: H
authors.initials: H
authors.lastname: Miwa
authors.forename: M
authors.initials: M
authors.lastname: Shikami
authors.forename: T
authors.initials: T
authors.lastname: Ikai
authors.forename: E
authors.initials: E
authors.lastname: Tajima
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: N
authors.initials: N
authors.lastname: Imai
authors.forename: A
authors.initials: A
authors.lastname: Hattori
authors.forename: T
authors.initials: T
authors.lastname: Kyo
authors.forename: M
authors.initials: M
authors.lastname: Watarai
authors.forename: K
authors.initials: K
authors.lastname: Miura
authors.forename: A
authors.initials: A
authors.lastname: Satoh
authors.forename: M
authors.initials: M
authors.lastname: Itoh
authors.forename: A
authors.initials: A
authors.lastname: Imamura
authors.forename: H
authors.initials: H
authors.lastname: Mihara
authors.forename: Y
authors.initials: Y
authors.lastname: Katoh
authors.forename: M
authors.initials: M
authors.lastname: Nitta
mesh_terms: D000328:Adult; D000368:Aged; D019898:Autocrine Communication / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004194:Disease; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D004791:Enzyme Inhibitors; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2