Tumor suppressor activity of the human consensus type I interferon gene.
Type I interferons have potent antiproliferative activity both in vitro 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 promoters (cytomegalovirus early promoter, murine metallothionein promoter and the Rous sarcoma virus LTR) were constructed and stably transfected into type I IFN-deficient myelogenous leukemic K562 cells. Constitutive expression of IFNcon1 reverted the malignant phenotype, as indicated by loss of tumorgenicity in nude mice. When stably transformed cells were mixed with parental tumor cells, there was retardation of tumor growth. Constitutive expression of IFNcon1 reverted the malignant phenotype in vitro, as indicated by growth inhibition in culture, and reduction in colony formation on soft agar. Furthermore, IFNcon1 gene expression resulted in elevated erythroid differentiation, growth arrest in S phase and induced apoptosis. Thus the presence of an active IFNcon1 gene overcomes the oncogenic potential of K562 by coordinated modulation of cell proliferation, differentiation and programmed cell death, and it acts as a tumor suppressor in vivo.
Geng
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Department of Biology, Indiana University, Bloomington 47405, USA.
Yu
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D
Blatt
L M
LM
Taylor
M W
MW
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D002899:Chromosomes, Human, Pair 9; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D016196:S Phase; D014162:Transfection; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D011993:Recombinant Fusion Proteins; D008668:Metallothionein