Ablation of transplanted HTLV-I Tax-transformed tumors in mice by antisense inhibition of NF-kappa B.
Mice transgenic for the human T cell leukemia virus (HTLV-I) Tax gene develop fibroblastic tumors that express NF-kappa B-inducible early genes. In vitro inhibition of NF-kappa B expression by antisense oligodeoxynucleotides (ODNs) inhibited growth of these culture-adapted Tax-transformed fibroblasts as well as an HTLV-I-transformed human lymphocyte line. In contrast, antisense inhibition of Tax itself had no apparent effect on cell growth. Mice treated with antisense to NF-kappa B ODNs showed rapid regression of transplanted fibrosarcomas. This suggests that NF-kappa B expression may be necessary for the maintenance of the malignant phenotype and provides a therapeutic approach for HTLV-I-associated disease.
Kitajima
I
I
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Shinohara
T
T
Bilakovics
J
J
Brown
D A
DA
Xu
X
X
Nerenberg
M
M
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use*
D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense