Reference SummaryChristofori G, Nature 1994 Jun 2;369(6479):414-8

Title

 A second signal supplied by insulin-like growth factor II in oncogene-induced tumorigenesis.

Authors

 Christofori G; Naik P; Hanahan D

Journal

 Nature

Volume

 369

Issue

 6479

Year

 1994

Pages

 414-8

Abstract

 Transgenic mice expressing the simian virus-40 large T-antigen (Tag) under the control of the insulin gene regulatory region offer a useful model for tumorigenesis. All the islets of Langerhans express Tag, although there is at first no aberrant proliferation. Over half of the islets become hyperplastic, however, and neovascularization of a further subset (about 10%)3 leads eventually to formation of highly vascularized solid tumours in 1-2% of islets by about 14 weeks of age. Here we show that the initial proliferative switch is correlated with focal activation of insulin-like growth factor II (IGF-II). Transfection with an antisense oligonucleotide to the IGF-II messenger RNA interferes with tumour cell proliferation in vitro, and transgenic mice homozygous for a disruption of the IGF-II gene develop tumours with reduced malignancy and a higher incidence of apoptosis. Several signals, in this case including an oncoprotein and a growth/survival factor, thus appear to be needed to elicit hyperproliferation.

Links

 J:76997 – MGI References
7910953 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6.Cg-Tg(RIP1-Tag)2Dh The genetic background was assumed to be backcrossed to C57BL/6 since C57BL/6J mice were used as controls.
[not specified]-Igf2tm1Rob Tg(RIP1-Tag)2Dh Lifespan ranges from 78-122 days.
The Igf2-/- mice used to create this strain have ~40% reduction in body mass.
[not specified]-Tg(RIP1-Tag)2Dh Lifespan ranges from 90-112 days.

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
[not specified]-Igf2tm1Rob Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell tumor Pancreas - Islet of Langerhans - Beta cell

observed
[not specified]-Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell tumor Pancreas - Islet of Langerhans - Beta cell

very high
C57BL/6J Pancreas - Islet of Langerhans - Beta cell tumor Pancreas - Islet of Langerhans - Beta cell

0
B6.Cg-Tg(RIP1-Tag)2Dh Pancreas - Islet of Langerhans - Beta cell tumor Pancreas - Islet of Langerhans - Beta cell

observed