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Constitutive nuclear factor-kappa B mRNA, protein overexpression and enhanced DNA-binding activity in thymidylate synthase inhibitor-resistant tumour cells

, : Constitutive nuclear factor-kappa B mRNA, protein overexpression and enhanced DNA-binding activity in thymidylate synthase inhibitor-resistant tumour cells. British Journal of Cancer 88(4): 624-629

In this study, the gene copy number, mRNA and protein expression levels and nuclear DNA-binding activity of nuclear factor kappa B (NF-kappa B) were compared in a panel of five pairs of thymidylate synthase (TS) inhibitor-resistant and wild-type parent cancer cell lines. High constitutive NF-kappa B DNA-binding activity was detected in all chemoresistant cell lines. The upregulated NF-kappa B activity was composed of NF-kappa B subunits p50 and p65. Four out of five resistant cell lines constitutively overexpressed NF-kappa B p50 and p65 mRNA and protein. One resistant cell line with the highest NF-kappa B DNA-binding activity showed normal p50 and p65 protein expression. No NF-kappa B gene amplification was detected in resistant cell lines. Transient exposure of wild-type RKO(WT) and H630(WT) cells to 5-FU induced NF-kappa B DNA-binding activity but had no effect on NF-kappa B protein expression in these cells. Our results indicate that high constitutive NF-kappa B activity caused by its gene overexpression is an intrinsic character of TS inhibitor-resistant cells. NF-kappa B can antagonise anticancer drug-induced apoptosis. High NF-kappa B expression and nuclear activity in TS inhibitor-resistant cancer cells may play an important role in the chemoresistance.


PMID: 12592379

DOI: 10.1038/sj.bjc.6600753

Other references

Ghosh, D., 1992: TFD: the transcription factors database. Nucleic Acids Research 20 Suppl: 2091-2093

Mey, W.; Botosaneanu, L., 1985: Glazial-refugiale Subspeziation von Psilopteryx psorosa s. l. (Kolenati, 1860) in den Karpaten und angrenzenden Mittelgebirgen Zentraleuropas (Trichoptera, Limnephilidae). Deutsche Entomologische Zeitschrift, 321-3: 109-127

Blanchard, R., 1907: Le paludisme a Madagascar. Archives de Parasitologie Paris, 11 185-214

Copenhaver, R.M.; Beinhocker, G.D., 1963: Evoked Occipital Potentials Recorded From Scalp Electrodes In Response To Focal Visual Illumination. Investigative Ophthalmology 2: 393-406

Evans, M.W., 2006: Modification of a local smoking ordinance: a case-report of chiropractic health advocacy. Health Promotion may involve assessing the community and assisting in the formation of coalitions that empower a community to reduce health risks. To describe an intervention lead by a doctor of chiropractic to reduce exposure to environmental tob...

Famaey, J.P.; Brooks, P.M.; Dick, W.C., 1975: Biological effects of nonsteroidal anti-inflammatory drugs. Seminars in Arthritis and Rheumatism 5(1): 63-81

Manabe, H., 1984: Analysis by HPLC of D-alanylglycine and its related compounds in rice plants. An amino acid mixture extracted from leaf blades of rice plants, which contained D-alanylglycine, was injected into an AA-pak cation exchange column, eluted according to the HC-095 method and analysed by HPLC. It was concluded that this method gav...

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