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Different cascades in the signaling pathway of two vascular endothelial growth factor (VEGF) receptors for the VEGF-mediated murine hepatocellular carcinoma development.
Oncol Rep. 2005 May; 13(5):853-7.OR

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.

Authors+Show Affiliations

The Third Department of Internal Medicine, Nara Medical University, Shijo-cho 840, Kashihara, Nara 634-8522, Japan. yoshijih@naramed-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15809749

Citation

Yoshiji, Hitoshi, et al. "Different Cascades in the Signaling Pathway of Two Vascular Endothelial Growth Factor (VEGF) Receptors for the VEGF-mediated Murine Hepatocellular Carcinoma Development." Oncology Reports, vol. 13, no. 5, 2005, pp. 853-7.
Yoshiji H, Noguchi R, Kuriyama S, 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. 2005;13(5):853-7.
Yoshiji, H., Noguchi, R., Kuriyama, S., Yoshii, J., Ikenaka, Y., Yanase, K., Namisaki, T., Kitade, M., Yamazaki, M., Uemura, M., & 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(5), 853-7.
Yoshiji H, 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. 2005;13(5):853-7. PubMed PMID: 15809749.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Different cascades in the signaling pathway of two vascular endothelial growth factor (VEGF) receptors for the VEGF-mediated murine hepatocellular carcinoma development. AU - Yoshiji,Hitoshi, AU - Noguchi,Ryuichi, AU - Kuriyama,Shigeki, AU - Yoshii,Junichi, AU - Ikenaka,Yasuhide, AU - Yanase,Koji, AU - Namisaki,Tadashi, AU - Kitade,Mitsuteru, AU - Yamazaki,Masaharu, AU - Uemura,Masahito, AU - Fukui,Hiroshi, PY - 2005/4/6/pubmed PY - 2005/9/30/medline PY - 2005/4/6/entrez SP - 853 EP - 7 JF - Oncology reports JO - Oncol Rep VL - 13 IS - 5 N2 - 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. SN - 1021-335X UR - https://www.unboundmedicine.com/medline/citation/15809749/Different_cascades_in_the_signaling_pathway_of_two_vascular_endothelial_growth_factor__VEGF__receptors_for_the_VEGF_mediated_murine_hepatocellular_carcinoma_development_ L2 - http://www.spandidos-publications.com/or/13/5/853 DB - PRIME DP - Unbound Medicine ER -