Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2003 Dec;94(12):1034-41.
doi: 10.1111/j.1349-7006.2003.tb01397.x.

Hepatoma-derived growth factor induces tumorigenesis in vivo through both direct angiogenic activity and induction of vascular endothelial growth factor

Yorihide Okuda  1 , Hideji Nakamura, Kenya Yoshida, Hirayuki Enomoto, Hirokazu Uyama, Tomonori Hirotani, Masanobu Funamoto, Hiroaki Ito, Allen D Everett, Toshikazu Hada, Ichiro Kawase
Affiliations

Hepatoma-derived growth factor induces tumorigenesis in vivo through both direct angiogenic activity and induction of vascular endothelial growth factor

Yorihide Okuda et al. Cancer Sci. 2003 Dec.

Abstract

Hepatoma-derived growth factor (HDGF) is highly expressed in tumor cells, and stimulates their proliferation. In the present study, we investigated the role of HDGF in tumorigenesis and elucidated the mechanism of action. Stable transfectants of NIH3T3 cells overexpressing HDGF did not show significant anchorage-independent growth in soft agar assay. However, these stable transfectants overexpressing HDGF generated sarcomatous tumors in nude mice. These tumors were red-colored macroscopically, and histologically showed a rich vascularity. Immunohistochemical analysis using CD31 antibody showed new vessel formation. Recombinant HDGF stimulated proliferation of human umbilical vein endothelial cells in a dose-dependent manner, and stimulated tubule formation. Furthermore, vascular endothelial growth factor (VEGF) was detected immunohistochemically in the tumor tissues. Transient expression of HDGF induced both VEGF gene and protein expression as demonstrated by a reporter assay using VEGF gene promoter. The administration of anti-VEGF neutralizing antibody significantly suppressed, but did not block, the tumor growth of HDGF-overexpressing cells in nude mice. Thus, these findings suggested that HDGF-induced tumor formation in vivo involves induction of VEGF as well as direct angiogenic activity.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R, Soltoff S. Oncogenes and signal transduction. Cell 1991; 64: 281–302. - PubMed
    1. Munger K. Disruption of oncogene/tumor suppressor networks during human carcinogenesis. Cancer Invest 2002; 20: 71–81. - PubMed
    1. Wakefield LM, Roberts AB. TGF‐beta signaling:positive and negative effects on tumorigenesis. Curr Opin Genet Dev 2002; 12: 22–29. - PubMed
    1. MacArthur CA, Lawshe A, Shankar DB, Heikinheimo M, Shackleford GM. FGF‐8 isoforms differ in NIH3T3 cell transforming potential. Cell Growth Differ 1995; 6: 817–25. - PubMed
    1. Vande Woude GF, Jeffers M, Cortner J, Alvord G, Tsarfaty I, Resau J. Met‐HGF/SF: tumorigenesis, invasion and metastasis. Ciba Found Symp 1997; 212: 119–30. - PubMed

MeSH terms

Substances

LinkOut - more resources