IFI16 inhibits tumorigenicity and cell proliferation of bone and cartilage tumor cells.
IFI16 is a member of the interferon-inducible p200-protein family, capable of modulating cell proliferation, and cellular senescence. In this study, these effects of IFI16 were studied in tumor cells derived from bone and cartilage. The level of IFI16 was markedly lower in human osteosarcomas as compared with its level in normal bone. Overexpression of functional IFI16 in human osteosarcoma and chondrosarcoma cell lines markedly inhibited colony formation, and significantly inhibited cell growth, an effect that could be reversed by introduction of gene specific siRNA into tumor cells. These inhibitory effects of IFI16 were associated with upregulation of p21 and inhibition of cyclin E, cyclin D1, c-Myc and Ras. In addition, ectopic expression of IFI16 in tumor cells increased senescence-associated beta-galactosidase and induced a senescence-like phenotype. In view of such effects, IFI16 might be a suitable target for therapeutic intervention in osteosarcoma and chondrosarcoma.
Zhang
Yan
Y
Department of Orthopaedic Surgery, New York University School of Medicine, New York, New York 10003, USA.
Howell
Ronald D
RD
Alfonso
Daniel T
DT
Yu
Jin
J
Kong
Li
L
Wittig
James C
JC
Liu
Chuan-ju
CJ
D017209:Apoptosis; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002813:Chondrosarcoma / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference; D018631:ras Proteins / Q000378:metabolism
C493956:CDKN1A protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; C489427:MYC protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D019938:Cyclin D1; C076700:IFI16 protein, human; D018631:ras Proteins