A. Kaba et al., LOCALIZATION AND STRUCTURE OF V-MOS IN TRANSFORMED MOUSE FIBROBLASTS REVERTED BY LONG-TERM INTERFERON TREATMENT TO NONMALIGNANCY, Journal of interferon & cytokine research, 17(12), 1997, pp. 739-746
We have reported previously that Moloney virus-transformed cells, when
treated for over 200 passages in the presence of low concentrations o
f mouse interferon-alpha/beta, can be reverted to a stable nonmalignan
t status. The cells recover full contact inhibition and are unable to
raise tumors when grafted in nude mice. In the present report, we show
that whether reverted or malignant, these cells contain deleted v-mos
oncogenes, which have lost 392 nucleotides. The truncated oncogenes c
ontain a reduced and modified open reading frame but are able, however
, to induce tumors when transfected in mouse 3T3 cells. As there is no
difference either in the location or in the structure of this modifie
d v-mos, whether yielded by reverted or malignant cells, we postulate
that both cell lines derive from the same population and this modifica
tion does not play any role in the reversion process obtained through
prolonged IFN-dependent selection. We suggest that reversion could be
an epigenetic phenomenon, involving the constitutive synthesis of IFN-
beta only in the reverted and not in the malignant cells. The continue
d persistence of such noncancerous cells could result at least partly
from a balance involving the expression of v-mos, IFN-beta, and an IFN
antagonist, sarcolectin. These reverted cells can undergo an unlimite
d number of passages, but they must be trypsinized before day 5 in con
fluent cultures. Thereafter, the cells stop dividing, cannot prolifera
te anymore, progressively show signs of apoptosis, and die.