TRANSGENIC mice expressing the simian virus-40 large T-antigen (Tag) u
nder the control of the insulin gene regulatory region offer a useful
model for tumorigenesis(1,2). All the islets of Langerhans express Tag
, although there is at first no aberrant proliferation. Over half of t
he islets become hyperplastic, however, and neovascularization of a fu
rther subset (about 10%)(3) leads eventually to formation of highly va
scularized solid tumours in 1-2% of islets by about 14 weeks of age. H
ere we show that the initial proliferative switch is correlated with f
ocal activation of insulin-like growth factor II (IGF-II). Transfectio
n with an antisense oligonucleotide to the IGF-II messenger RNA interf
eres with tumour cell proliferation in vitro, and transgenic mice homo
zygous for a disruption of the IGF-II gene develop tumours with reduce
d 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.