[NF-kappa B and cancers].
The NF-kappa B transcription factor controls the expression of many genes, including genes regulating cell proliferation or survival and involved in oncogenesis. We showed that many breast cancers express high levels of the NF-kappa B inhibitor p100. In these cells, p100 sequesters NF-kappa B in the cytoplasm and blocks the induction of NF-kappa B-dependent genes in response to stimuli such as TNF-alpha. We also demonstrated that the mechanisms controlling NF-kappa B activity in adenocarcinoma cells differ from those observed in lymphoid cells. Finally, we showed that NF-kappa B was activated in response to chemotherapeutic drugs. However, this activation does not modify p53 induction or the cytotoxic response in the cell lines we have analyzed. Gene therapy is a novel approach for cancer treatment. We evaluated a gene therapy strategy combining a suicide genes and cytokine genes in a model of peritoneal carcinomatosis induced by colorectal cancer cells (DHD/K12 cells). In vitro transduction of the HSV-TK suicide gene in DHD/K12 cells, sensitize them to ganciclovir cytotoxicity. We also obtained a therapeutic effect by in vivo transduction of the TK gene in animals which had developed a peritoneal carcinomatosis. This therapeutic effect was further enhanced by simultaneous administration of genes coding for the IL-12 or GM-CSF cytokines.
Bours
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D000230:Adenocarcinoma / Q000235:genetics* / Q000628:therapy*; D001943:Breast Neoplasms / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000628:therapy*; D016207:Cytokines / Q000235:genetics; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016328:NF-kappa B / Q000235:genetics*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D016328:NF-kappa B