Jh. Yim et al., Enhancing in vivo tumorigenicity of B16 melanoma by overexpressing interferon regulatory factor-2: Resistance to endogenous IFN-gamma, J INTERF CY, 19(7), 1999, pp. 723-729
We investigated the role of interferon (IFN) regulatory factor-2 (IRF-2) as
an oncoprotein in vivo, opposing endogenous IFN-gamma suppression of tumor
growth. Using syngeneic IFN-gamma knockout mice, we show that endogenous I
FN-gamma slows growth of the mouse melanoma cell line B16-F10 in immunocomp
etent mice, suggesting that tumor cell resistance to IFN-gamma may lead to
greater tumorigenicity, IRF-2 is a nuclear transcription factor induced by
IFN-gamma that represses numerous IFN-inducible genes, including genes that
regulate cell growth, in opposition to the transcriptional activator IRF-1
, B16-F10 has a marked growth inhibitory response to IFN-gamma in vitro and
has very little IRF-2 induction compared with other murine tumor cell line
s. We engineered B16-F10 cells to stably overexpress murine IRF-2., In vitr
o, these transfected cells showed a marked resistance to the growth-inhibit
ory effect of IFN-gamma, In normal mice the IRF-2-transfected cells grew mu
ch faster than control tumors. In syngeneic IFN-gamma knockout mice, contro
l cells grew at a rate similar to that of IRF-2-transfected cells, implicat
ing resistance to endogenous IFN-gamma as playing the major role in enhance
d growth of IRF-2-transfected tumors in intact mice. These experiments demo
nstrate that (1) IRF-2 enhances B16 melanoma growth and increases resistanc
e to IFN-gamma in vitro, and (2) IRF-2 opposes the growth suppression media
ted by endogenous IFN-gamma in vivo.