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Blood, Vol. 96 No. 1 (July 1), 2000:
pp. 259-263
Overexpression of murine fizzy-related
(fzr) increases natural killer cell-mediated cell death and
suppresses tumor growth
Chun-Xiang Wang,
Bernard C. Fisk,
Madhuri Wadehra,
Helen Su, and
Jonathan Braun
From the Department of Pathology and Laboratory Medicine, University
of California, Los Angeles, School of Medicine and
Jonsson Comprehensive Cancer Center, and Molecular Biology Institute,
Los Angeles, CA.
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.
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