GROWTH AND REJECTION PATTERNS OF MURINE LYMPHOMA CELLS ANTIGENICALLY ALTERED FOLLOWING DRUG TREATMENT IN VIVO

Abstract Deregulated c-MYC is found in a variety of cancers where it promotes proliferation as well as apoptosis. In many hematologic malignancies, enhanced NF-κB exerts prosurvival functions. Here we investigated the role of NF-κB in mouse and human c-MYC–transformed lymphomas. The NF-κB pathway is extinguished in murine lymphoma cells, and extrinsic stimuli typically inducing NF-κB activity fail to activate this pathway. Genetic activation of the NF-κB pathway induces apoptosis in these cells, whereas inhibition of NF-κB by an IκBα superrepressor provides a selective advantage in vivo. Furthermore, in human Burkitt lymphoma cells we find that NF-κB activation induces apoptosis. NF-κB up-regulates Fas and predisposes to Fas-induced cell death, which is caspase-8 mediated and can be prevented by CFLAR overexpression. We conclude that c-MYC overexpression sensitizes cells to NF-κB–induced apoptosis, and persistent inactivity of NF-κB signaling is a prerequisite for MYC-mediated tumorigenesis. We could also show that low immunogenicity and Fas insensitivity of MYC-driven lymphoma cells are reversed by activation of NF-κB. Our observations provide a molecular explanation for the described absence of the NF-κB signaling in Burkitt lymphoma and question the applicability of NF-κB inhibitors as candidates for treatment of this cancer.

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A Quantitative Assay for the Number of Murine Lymphoma Cells capable of Proliferation in vivo

Nature ◽

10.1038/199079a0 ◽

1963 ◽

Vol 199 (4888) ◽

pp. 79-80 ◽

Cited By ~ 240

Author(s):

W. R. BRUCE ◽

H. VAN DER GAAG

Keyword(s):

Quantitative Assay ◽

Lymphoma Cells ◽

Murine Lymphoma

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Secondary Cytotoxic Response In Vitro Against Moloney Lymphoma Cells Antigenically Altered by Drug Treatment In Vivo

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/60.1.109 ◽

1978 ◽

Vol 60 (1) ◽

pp. 109-112 ◽

Cited By ~ 13

Author(s):

Angela Santoni ◽

Yvonne Kinney ◽

Abraham Goldin

Keyword(s):

Drug Treatment ◽

Lymphoma Cells ◽

Cytotoxic Response

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Ultrastructural changes in murine lymphoma cells exposed to ultraviolet-A radiation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010008482x ◽

1991 ◽

Vol 49 ◽

pp. 104-105

Author(s):

Delma P. Thomas ◽

Dianne E. Godar

Keyword(s):

Medical Devices ◽

Blood Cells ◽

White Blood Cells ◽

Consumer Products ◽

Ultrastructural Changes ◽

Ultraviolet A ◽

Uv Spectrum ◽

Lymphoma Cells ◽

Murine Lymphoma ◽

Transmission Electron

Ultraviolet radiation (UVR) from all three waveband regions of the UV spectrum, UVA (320-400 nm), UVB (290-320 nm), and UVC (200-290 nm), can be emitted by some medical devices and consumer products. Sunlamps can expose the blood to a considerable amount of UVR, particularly UVA and/or UVB. The percent transmission of each waveband through the epidermis to the dermis, which contains blood, increases in the order of increasing wavelength: UVC (10%) < UVB (20%) < UVA (30%). To investigate the effects of UVR on white blood cells, we chose transmission electron microscopy to examine the ultrastructure changes in L5178Y-R murine lymphoma cells.

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