Reference SummaryInoue M, Cancer Cell 2002 Mar;1(2):193-202
Title |
VEGF-A has a critical, nonredundant role in angiogenic switching and pancreatic beta cell carcinogenesis. | ||||
Authors |
Inoue M; Hager JH; Ferrara N; Gerber HP; Hanahan D | ||||
Journal |
Cancer Cell | ||||
Volume |
1 | ||||
Issue |
2 | ||||
Year |
2002 | ||||
Pages |
193-202 | ||||
Abstract |
In the RIP1-Tag2 mouse model of pancreatic islet carcinoma, angiogenesis is switched on in a discrete premalignant stage of tumor development, persisting thereafter. Signaling through VEGF receptor tyrosine kinases is a well-established component of angiogenic regulation. We show that five VEGF ligand genes are expressed in normal islets and throughout islet tumorigenesis. To begin dissecting their contributions, we produced an islet beta cell specific knockout of VEGF-A, resulting in islets with reduced vascularity but largely normal physiology. In RIP1-Tag2 mice wherein most oncogene-expressing cells had deleted the VEGF-A gene, both angiogenic switching and tumor growth were severely disrupted, as was the neovasculature. Thus, VEGF-A is crucial for angiogenesis in a prototypical model of carcinogenesis, whose loss is not readily compensated. | ||||
Links |
J:77131 – MGI References 12086877 – National Library of Medicine/PubMed |
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Strain Notes
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| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| B6.Cg-Tg(RIP1-Tag)2Dh | Pancreas - Islet of Langerhans - Beta cell hyperplasia | Pancreas - Islet of Langerhans - Beta cell |
observed |
||
| C57BL/6J-Tg(RIP1-Tag)2Dh Vegfatm2Gne | Pancreas - Islet of Langerhans - Beta cell hyperplasia | Pancreas - Islet of Langerhans - Beta cell |
100 |
||
| C57BL/6J-Tg(RIP1-Tag)2Dh Tg(Ins2-cre)25Mgn Vegfatm2Gne/+ | Pancreas - Islet of Langerhans - Beta cell hyperplasia | Pancreas - Islet of Langerhans - Beta cell |
very high |
||
| C57BL/6J-Tg(RIP1-Tag)2Dh Tg(Ins2-cre)25Mgn Vegfatm2Gne | Pancreas - Islet of Langerhans - Beta cell hyperplasia | Pancreas - Islet of Langerhans - Beta cell |
observed |
||
| B6.Cg-Tg(RIP1-Tag)2Dh | Pancreas - Islet of Langerhans - Beta cell tumor | Pancreas - Islet of Langerhans - Beta cell |
observed |
||
| C57BL/6J-Tg(RIP1-Tag)2Dh Vegfatm2Gne | Pancreas - Islet of Langerhans - Beta cell tumor | Pancreas - Islet of Langerhans - Beta cell |
100 |
||
| C57BL/6J-Tg(RIP1-Tag)2Dh Tg(Ins2-cre)25Mgn Vegfatm2Gne/+ | Pancreas - Islet of Langerhans - Beta cell tumor | Pancreas - Islet of Langerhans - Beta cell |
100 |
||
| C57BL/6J-Tg(RIP1-Tag)2Dh Tg(Ins2-cre)25Mgn Vegfatm2Gne | Pancreas - Islet of Langerhans - Beta cell tumor | Pancreas - Islet of Langerhans - Beta cell |
observed |
||
| C57BL/6J-Tg(RIP1-Tag)2Dh Tg(Ins2-cre)25Mgn | Pancreas - Islet of Langerhans - Beta cell tumor | Pancreas - Islet of Langerhans - Beta cell |
observed |