Different cascades in the signaling pathway of two vascular endothelial growth factor (VEGF) receptors for the VEGF-mediated murine hepatocellular carcinoma development

  • Authors:
    • Hitoshi Yoshiji
    • Ryuichi Noguchi
    • Shigeki Kuriyama
    • Junichi Yoshii
    • Yasuhide Ikenaka
    • Koji Yanase
    • Tadashi Namisaki
    • Mitsuteru Kitade
    • Masaharu Yamazaki
    • Masahito Uemura
    • Hiroshi Fukui
  • View Affiliations

  • Published online on: May 1, 2005     https://doi.org/10.3892/or.13.5.853
  • Pages: 853-857
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

It has been shown that the interaction between the potent angiogenic factor; the vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1 and VEGFR-2), plays a pivotal role in tumor development, including hepatocellular carcinoma (HCC). However, the properties of the respective VEGF receptor in the signaling transduction pathway of VEGF-mediated effects in HCC have not been elucidated yet. The aim of this study was to examine the respective signaling pathway of two VEGFRs in the VEGF-mediated murine HCC development and angiogenesis. We examined the signaling cascades of VEGFR-1 and VEGFR-2 in the VEGF-mediated HCC development in combination with a retroviral tetracycline (tet)-regulated (Retro-Tet) gene expression system, which can manipulate the gene expression in vivo by providing tet in the drinking water, as well as VEGFR-1 and VEGFR-2 specific neutralizing monoclonal antibodies (R-1mAb and R-2mAb, respectively). Both R-1mAb and R-2mAb significantly suppressed the VEGF-mediated tumor growth associated with reduction of the tumoral neovascularization, and the combination treatment with both mAbs almost completely attenuated the tumor development and angiogenesis. The protein kinase-C (PKC) and MEK1/2 activities in the tumor were markedly attenuated by treatment with R-2mAb, whereas R-1mAb did not alter these activities. These results suggested that both VEGFR-1 and VEGFR-2 play important roles, and lie in the different signaling cascades by which VEGF augments HCC development and angiogenesis.

Related Articles

Journal Cover

May 2005
Volume 13 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Yoshiji H, Noguchi R, Kuriyama S, Yoshii J, Ikenaka Y, Yanase K, Namisaki T, Kitade M, Yamazaki M, Uemura M, Uemura M, et al: Different cascades in the signaling pathway of two vascular endothelial growth factor (VEGF) receptors for the VEGF-mediated murine hepatocellular carcinoma development. Oncol Rep 13: 853-857, 2005.
APA
Yoshiji, H., Noguchi, R., Kuriyama, S., Yoshii, J., Ikenaka, Y., Yanase, K. ... Fukui, H. (2005). Different cascades in the signaling pathway of two vascular endothelial growth factor (VEGF) receptors for the VEGF-mediated murine hepatocellular carcinoma development. Oncology Reports, 13, 853-857. https://doi.org/10.3892/or.13.5.853
MLA
Yoshiji, H., Noguchi, R., Kuriyama, S., Yoshii, J., Ikenaka, Y., Yanase, K., Namisaki, T., Kitade, M., Yamazaki, M., Uemura, M., Fukui, H."Different cascades in the signaling pathway of two vascular endothelial growth factor (VEGF) receptors for the VEGF-mediated murine hepatocellular carcinoma development". Oncology Reports 13.5 (2005): 853-857.
Chicago
Yoshiji, H., Noguchi, R., Kuriyama, S., Yoshii, J., Ikenaka, Y., Yanase, K., Namisaki, T., Kitade, M., Yamazaki, M., Uemura, M., Fukui, H."Different cascades in the signaling pathway of two vascular endothelial growth factor (VEGF) receptors for the VEGF-mediated murine hepatocellular carcinoma development". Oncology Reports 13, no. 5 (2005): 853-857. https://doi.org/10.3892/or.13.5.853