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.
Keywords
CarcinogenesisTransgeneCancer researchGrowth factorBiologyGenetically modified mouseTransfectionOncogeneCell growthInsulin-like growth factorMolecular biologyCell biologyGeneReceptorCell cycleGenetics
MeSH Terms
AnimalsAntigensPolyomavirus TransformingApoptosisBase SequenceCell DivisionCell TransformationNeoplasticIn Situ HybridizationInsulinInsulin-Like Growth Factor IIInsulinomaMiceMiceInbred C57BLMiceTransgenicMolecular Sequence DataNuclear ProteinsOligodeoxyribonucleotidesOncogenesPancreatic NeoplasmsProliferating Cell Nuclear AntigenRNAAntisenseRegulatory SequencesNucleic AcidSignal TransductionTumor CellsCultured
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Publication Info
- Year
- 1994
- Type
- article
- Volume
- 369
- Issue
- 6479
- Pages
- 414-418
- Citations
- 390
- Access
- Closed
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Cite This
Gerhard Christofori,
Paul Naik,
Douglas Hanahan
(1994).
A second signal supplied by insulin-like growth factor II in oncogene-induced tumorigenesis.
Nature
, 369
(6479)
, 414-418.
https://doi.org/10.1038/369414a0
Identifiers
- DOI
- 10.1038/369414a0
- PMID
- 7910953