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 tumorigenesis1,2. All the islets of Langerhans express Tag, although there is at first no aberrant proliferation. Over half of the islets become hyperplastic, however, and neovascu-larization 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 prolifer-ative switch is correlated with focal activation of insulin-like growth factor II (IGF-II). Transfection with an antisense oligo-nucleotide 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.
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Christofori, G., Naik, P. & Hanahan, D. A second signal supplied by insulin-like growth factor II in oncogene-induced tumorigenesis. Nature 369, 414–418 (1994). https://doi.org/10.1038/369414a0
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DOI: https://doi.org/10.1038/369414a0
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