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A potential role for vascular endothelial growth factor-D as an autocrine growth factor for human breast carcinoma cells.

AbstractBACKGROUND:
Vascular endothelial growth factor-D (VEGF-D) binds and activates vascular endothelial growth factor receptor-2 (VEGFR-2), which signals for angiogenesis, and VEGFR-3, which signals for lymphangiogenesis. Besides endothelial cells, VEGFR-2 has been detected on malignant cells, including human breast carcinoma cells.
MATERIALS AND METHODS:
It was examined if ectopic expression of human VEGF-D affected growth of breast carcinoma cell lines in vitro and in vivo.
RESULTS:
VEGF-D overexpressing clonal MCF-7 and MDA-MB-231 cell lines displayed increased proliferative activities and upregulation of cyclins A, D1 and D3, compared to the vector control. Following subcutaneous inoculation of the MDA-MB-231 cells into nude mice, growth of the VEGF-D overexpressing cells was greatly accelerated. The tumor weight gain was accompanied by increased proliferative activity, cyclin A expression and microvascular density.
CONCLUSIONS:
These findings suggest that VEGF-D functions both as an autocrine growth factor and a stimulator of angiogenesis in breast cancer.
AuthorsManabu Akahane, Takemi Akahane, Amy Shah, Eijiro Okajima, Unnur P Thorgeirsson
JournalAnticancer research (Anticancer Res) 2005 Mar-Apr Vol. 25 Issue 2A Pg. 701-7 ISSN: 0250-7005 [Print] Greece
PMID15868899 (Publication Type: Journal Article)
Chemical References
  • CCND3 protein, human
  • Ccnd3 protein, mouse
  • Cyclin A
  • Cyclin D3
  • Cyclins
  • DNA, Complementary
  • Vascular Endothelial Growth Factor D
  • Cyclin D1
Topics
  • Animals
  • Blotting, Western
  • Breast Neoplasms (blood supply, genetics, metabolism, pathology)
  • Carcinoma (blood supply, genetics, metabolism, pathology)
  • Cell Growth Processes (physiology)
  • Cell Line, Tumor
  • Cyclin A (biosynthesis, genetics)
  • Cyclin D1 (biosynthesis, genetics)
  • Cyclin D3
  • Cyclins (biosynthesis, genetics)
  • DNA, Complementary (genetics)
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic (metabolism, pathology)
  • Transfection
  • Up-Regulation
  • Vascular Endothelial Growth Factor D (biosynthesis, genetics, physiology)

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