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Extinction and activation of the thyroglobulin promoter in hybrids of differentiated and transformed thyroid cells.

机译:甲状腺球蛋白启动子在分化和转化的甲状腺细胞杂种中的灭绝和激活。

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Thyroglobulin gene expression was repressed in a rat thyroid cell line transformed with Kirsten murine sarcoma virus. Expression of a dominant selectable marker driven by the thyroglobulin promoter was also inhibited. Somatic cell hybridization of transformed and differentiated thyroid cells resulted in extinction of thyroglobulin gene expression. When transformed cells carrying a dominant selectable marker driven by the thyroglobulin promoter were fused to differentiated cells and expression of this marker was selected, we obtained stable hybrid cell lines expressing both the endogenous and the exogenous thyroglobulin promoters. Although the expression of v-ras remained unchanged compared with expression in the parental transformed cells, transformation was suppressed in the hybrid cell lines. The other thyroid differentiation markers, iodide uptake and thyroid-stimulating hormone-dependent growth, were inhibited in all the hybrids tested. We show that activity of the thyroglobulin promoter correlates with the presence of a thyroid nuclear factor that binds the promoter at position -60 from the transcription start site. Loss of this factor accompanies the extinction of thyroglobulin gene expression in hybrids selected for expression of a non-thyroid-specific promoter.
机译:在用Kirsten鼠肉瘤病毒转化的大鼠甲状腺细胞系中,甲状腺球蛋白基因表达受到抑制。也抑制了由甲状腺球蛋白启动子驱动的显性选择标记的表达。转化和分化的甲状腺细胞的体细胞杂交导致甲状腺球蛋白基因表达的消失。当将携带由甲状腺球蛋白启动子驱动的显性选择标记的转化细胞融合至分化的细胞并选择该标记的表达时,我们获得了稳定表达内源性和外源性甲状腺球蛋白启动子的杂交细胞系。尽管与亲本转化细胞中的表达相比,v-ras的表达保持不变,但是在杂交细胞系中转化被抑制。在所有测试的杂种中,其他甲状腺分化标志物,碘化物摄取和促甲状腺激素依赖性生长受到抑制。我们显示甲状腺球蛋白启动子的活性与甲状腺核因子的存在相关,该因子与转录起始位点-60处的启动子结合。在选择用于表达非甲状腺特异性启动子的杂种中,甲状腺球蛋白基因表达的消失伴随着该因子的丧失。

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