M. Sagara et al., ACTIVATION OF THE NUCLEAR ONCOGENES N-MYC AND C-JUN IN CARTINOID TUMORS OF TRANSGENIC MICE CARRYING THE HUMAN ADENOVIRUS-TYPE-12 E1 REGION GENE, DNA and cell biology, 14(2), 1995, pp. 95-101
The adenovirus (Ad) El region genes, EIA and E1B, are well known coope
ratively to transform primary rodent cells and activate a number of ce
llular promoters, including nuclear oncogenes such as N-myc and c-jun,
in transfected cell lines. However, there is still less information a
vailable on the in vivo mechanism(s) by which the El region gene, when
chromosomally integrated ill the living animals, exerts its effect on
nuclear oncogene activation coupled with transformation. To investiga
te such in vivo activity of E1A we have used a series of microinjectio
n experiments into fertilized eggs to generate three transgenic mice c
arrying the Ad12-type E1A/E1B genes under the control of the human ren
in gene, This transgene caused an early onset of bowel cartinoid tumor
s that express neural cell adhesion molecules, but do not metastasize
to any region. Northern blot analysis revealed that the transgenes wer
e considerably expressed in the tumors, but not in other tissues at de
tectable levels. Interestingly, the levels of N-myc and c-jun mRNAs in
the cartinoid tumors were elevated 19- and 8-fold, respectively, as c
ompared with those found in the control intestine. In contrast, the ma
jor histocompatibility complex (MHC) class I mRNA level was not altere
d between the tumor and control intestines, suggesting that this uncha
nged expression may reflect the loss of tumor metastasis. These findin
gs provide the first in vivo evidence that the expression of the Ad12
El region gene induces cartinoid tumors associated with the activation
of the nuclear oncogenes N-mye and c-jun.