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Angiotensinogen delays angiogenesis and tumor growth of hepatocarcinoma in transgenic mice.
- Source :
-
Cancer research [Cancer Res] 2009 Apr 01; Vol. 69 (7), pp. 2853-60. Date of Electronic Publication: 2009 Mar 24. - Publication Year :
- 2009
-
Abstract
- Angiotensinogen, a member of the serpin family, is involved in the suppression of tumor growth and metastasis. To investigate whether human angiotensinogen protects against tumor progression in vivo, we established an original bitransgenic model in which transgenic mice expressing human angiotensinogen (Hu-AGT-TG mice) were crossed with a transgenic mouse model of hepatocellular carcinoma (HCC-TG mice). Bitransgenic mice overexpressing human angiotensinogen (HCC/Hu-AGT-TG) had a significantly longer survival time than the HCC-TG mice and a reduction of both tumor growth and blood flow velocities in the liver. This antitumor effect of angiotensinogen is related to a reduced angiogenesis, impaired expression of endothelial arterial markers (active Notch4, Delta-like 4 ligand, and ephrin B2) with a decrease of arterial vessel density in HCC/Hu-AGT-TG mice liver. Overexpression of human angiotensinogen decreases angiogenesis, and prevents tumor sinusoids from remodeling and arterialization, thus delaying tumor progression in vivo.
- Subjects :
- Adaptor Proteins, Signal Transducing
Angiotensinogen biosynthesis
Angiotensinogen blood
Angiotensinogen genetics
Animals
Calcium-Binding Proteins
Cell Growth Processes physiology
Ephrin-B2 biosynthesis
Female
Humans
Intracellular Signaling Peptides and Proteins
Liver metabolism
Liver pathology
Liver Neoplasms, Experimental genetics
Liver Neoplasms, Experimental metabolism
Liver Neoplasms, Experimental pathology
Male
Membrane Proteins biosynthesis
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neovascularization, Pathologic genetics
Neovascularization, Pathologic metabolism
Neovascularization, Pathologic pathology
Proto-Oncogene Proteins biosynthesis
RNA, Messenger biosynthesis
RNA, Messenger genetics
Receptor, Notch4
Receptors, Notch biosynthesis
Angiotensinogen metabolism
Liver Neoplasms, Experimental blood supply
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 69
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 19318581
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-08-2484