trans activation of nerve growth factor in transgenic mice containing the human T-cell lymphotropic virus type I tax gene.
Three lines of transgenic mice containing the human T-cell lymphotropic virus type I (HTLV-I) tax gene develop neurofibromas composed of perineural fibroblasts (S. H. Hinrichs, M. Nerenberg, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1340-1343, 1987; M. Nerenberg, S. H. Hinrichs, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1324-1327, 1987). Tumors and tumor cell lines derived from these mice produce neurite outgrowth from PC-12 cells and nerve growth factor (NGF), as determined by RNA (Northern) blot analysis and enzyme-linked immunosorbent assays. In vitro cotransfection studies demonstrate that Tax is able to trans activate the NGF promoter in NIH 3T3 fibroblast cells. The major cis-acting tax-responsive element in the NGF promoter (AGGGTGTGACGA) has 92% homology with a tax-responsive element contained within the 21-bp repeats of the HTLV-I long terminal repeat. The receptor for NGF is also expressed in the transgenic tumor cells, suggesting that Tax may activate an autocrine mechanism through the upregulation of NGF.
Green
J E
JE
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland 21702-1201.
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA; D004252:DNA Mutational Analysis; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics*; D009455:Neurofibroma; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D009414:Nerve Growth Factors; D004247:DNA