WASHINGTON _ Interferon, the once-touted "magic bullet"therapy for infectious disease and cancer, does play a key role in theregulation of the cell cycle and the development of human cancer, aJapanese researcher reported Tuesday.Tadatsugu Taniguchi, of the Institute for Molecular and CellularBiology at Osaka University, told the Human Genome 1994conference that highly specialized forms of these substances eitherinhibit or promote cell growth.The research suggests that interferon, used appropriately, ultimatelymay prove to be the basis for anti-cancer therapy, despite thedashed hopes of a decade ago."The mixture of hope and disappointment 10 years ago occurredprincipally because we knew too little about interferon's function,"the researcher said. "Now we know more."Taniguchi, whose research effort included specific contributions byresearchers in Canada and the United States, has examined thesefunctions in a series of experiments involving nude mice and humancancer patients."When we started these studies we were not aware of howinterferon might regulate oncogenesis," Taniguchi said.Previous studies have shown that interferon is produced by a subsetof white blood cells known as T-lymphocytes, which can bestimulated to churn out interferon by infection or tumor growth.Taniguchi's research has shown that interferon's action depends ontwo competing chemical throttles known as interferon-regulatoryfactor 1 (IRF-1) and interferon-regulatory factor 2 (IRF-2). IRF-1 isa growth activator; its competitor, IRF-2, is a growth inhibitor."IRF-1 cannot activate when the two factors are expressedtogether," he said, "suggesting that IRF-2 acts as repressor."In a healthy individual, the two factors operate in concert tomodulate cell growth so that it doesn't spiral out of control."Growth factors are important, but it is always just as important thatgrowth is controlled," Taniguchi said.In one set of experiments, Taniguchi manipulated expression ofIRF-1 in nude mice. "We made cells that over-express IRF-1," hesaid. "They promoted tumor growth. These cells have oncogeniccapacity just by over-expression."When the researchers introduced cells designed to produce excessIRF-1 and IRF-2, the balance was restored, he said, and the micedid not develop excess tumors.Studies of 13 human cancer patients suggested another mechanismfor IRF-1-related tumor growth. All of the patients had leukemia orpre-leukemic myelodysplastic syndromes, he said.Tanaguchi found that each patient had at least one faulty version ofthe IRF-1 gene, suggesting that the absence of inhibitory IRFallowed cell growth to spiral out of control.But further study of the human IRF-1 genes suggested anotherpossible explanation, Taniguchi said. "By analyzing some of theabnormalities, we noted this region [the IRF-1 gene] undergoesexon skipping at a very high frequency. This doesn't occur in themouse IRF-1."The reason the IRF-1 gene does not function is not known, he said,but it appears to contribute to carcinogenesis. n
-- Steve Sternberg Special to BioWorld Today
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