TUMOR-SUPPRESSOR ACTIVITY OF THE HUMAN CONSENSUS TYPE-I INTERFERON GENE

Type I interferons have potent antiproliferatlve activity both in vitr o and in vivo, and their tumor suppressor activity has been suggested. A series of eukaryotic vectors containing a synthetic human consensus type I interferon gene (IFN-con1) under the control of different prom oters (cytomegalovirus early promoter, murine metallothionein promoter and the Rous sarcoma virus LTR) were constructed and stably transfect ed Into type I IFN-deficient myelogenous leukemic K562 cells. Constitu tive expression of IFNcon1 reverted the malignant phenotype, as indica ted by loss of tumorgenicity in nude mice. When stably transformed cel ls were mixed with parental tumor cells, there was retardation of tumo r growth. Constitutive expression of IFNcon1 reverted the malignant ph enotype In vitro, as indicated by growth inhibition in culture, and re duction in colony formation on soft agar. Furthermore, IFNcon1 gene ex pression resulted in elevated erythroid differentiation, growth arrest in S phase and induced apoptosis. Thus the presence of an active IFNc on1 gene overcomes the oncogenic potential of K562 by coordinated modu lation of cell proliferation, differentiation and programmed cell deat h, and it acts as a tumor suppressor in vivo.