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

Strain Notes

Strain Note
C57BL/6J-Tg(RIP1-Tag)2Dh Tg(Ins2-cre)25Mgn Vegfatm2Gne Expression of Vegfa was deleted in ~85% of pancreatic beta cells via cre recombination of the floxed Vegfa allele.

Models

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