© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 22, 1956-1960,
November 17, 1999
© 1999 Oxford University Press
REPORTS |
Inhibition of NF-
B, Clonogenicity, and Radiosensitivity of Human Cancer Cells
Affiliation of authors: Department of Radiation Oncology, Experimental Division, University of California at Los Angeles School of Medicine.
Correspondence to: Frank Pajonk, M.D., Ph.D., Department of Radiation Oncology, Roy E. Coats Research Laboratories, University of California at Los Angeles School of Medicine, 10833 Le Conte Ave., Los Angeles, CA 90095-1714 (e-mail: fpajonk{at}ucla.edu).
BACKGROUND: Activation of the transcription factor NF-
B is part of the immediate early
response of tissues to ionizing irradiation. This pathway has been shown to protect cells from
tumor necrosis factor-
, chemotherapy, and radiation therapy-induced apoptosis
(programmed cell death). However, because the role of NF-B as a modifier of the intrinsic
radiosensitivity of cancer cells is less clear, we have studied the impact of NF-B on the
intrinsic radiosensitivity of human cancer cells. METHODS: We used PC3 prostate cancer cells
and HD-MyZ Hodgkin's lymphoma cells transduced with an adenovirus vector that
contains a gene encoding a form of IB (an inhibitor of NF-B) that cannot be
phosphorylated. This form of IB will remain bound to NF-B; thus, NF-B cannot
be activated. We monitored NF-B activity with a gel-shift assay and used a colony-forming
assay to assess clonogenicity and radiosensitivity. RESULTS: Constitutive DNA-binding activity
of NF-B was dramatically decreased in PC3 cells transduced with the IB
super-repressor gene. The clonogenicity of transduced PC3 cells declined to 19.6% of that
observed for untreated control cells, a finding similar to one we have previously demonstrated for
IB-transduced HD-MyZ cells. However, inhibition of NF-B activity in the surviving
PC3 and HD-MyZ cells failed to alter their intrinsic radiosensitivity. CONCLUSIONS: We
conclude that activation of NF-B does not determine the intrinsic radiosensitivity of cancer
cells, at least for the cell lines tested in this study.
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