Overexpression of murine fizzy-related (fzr) increases natural killer cell-mediated cell death and suppresses tumor growth.
Fizzy-related (fzr) is a recently identified 7WD domain family member implicated in cell cycle regulation of Drosophila and yeast. In this study, the murine homologue of fzr was isolated by suppression subtractive hybridization as a gene with decreased expression during malignant progression of a murine B-lymphoma cell line. Retroviral overexpression of fzr in B-lymphoma cells reduced tumor formation. Those tumors that did arise had diminished or extinguished retroviral Fzr. Surprisingly, fzr overexpression dramatically increased B-lymphoma cell susceptibility to natural killer cell (NK) cytotoxicity, a host-resistant mechanism for tumor formation in this model system. These findings implicate fzr as a new category of genes suppressing B-cell tumorigenesis and suggest a novel role for fzr in the target cell interaction with NK cells.
Wang
C X
CX
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095-1732, USA.
Fisk
B C
BC
Wadehra
M
M
Su
H
H
Braun
J
J
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000276:immunology*; D002455:Cell Division; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004330:Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D011230:Precancerous Conditions / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C577585:Fzr1 protein, mouse; D019476:Insect Proteins; C577674:fzr protein, Drosophila