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首页> 外文期刊>Cellular and Molecular Neurobiology >Distinct patterns of gene expression induced by viral oncogenes in human embryonic brain cells.
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Distinct patterns of gene expression induced by viral oncogenes in human embryonic brain cells.

机译:病毒致癌基因在人类胚胎脑细胞中诱导的基因表达的不同模式。

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1. The limited lifespan of human embryonic brain (HEB) cells hampers their therapeutic use for the treatment of neurodegenerative diseases. 2. Stable expression of SV40 large T antigen (LTA) or E6E7 genes of human papillomavirus type 16 significantly increased the lifespan of HEB cells, but did not induce transformation. 3. The extended lifespan was triggered by changes in the expression of antiproliferative genes. We found that changes in the expression of p16 (INK4a), p21 (WAFI), p14ARF, and p53 tumor suppressor gene, but not p27 (Kip1), differed between the LTA- and E6E7-HEB cells. 4. Despite the induction of p53 RNA, p53 protein was undetectable in HEB-E6E7 cells. In contrast, p53 protein was increased in HEB-LTA cells as compared with the parental cells. Expression of p21 was, however, reduced in both cell lines. 5. While p16 was decreased in HEB-E6E7 cells, its expression was increased in HEB-LTA cells. 6. Despite these changes, HEB cell lines showed neuron-like morphological differentiation whenthe intracellular level of cAMP was elevated. 7. This suggests that the mechanisms for inducing neuronal differentiation are still intact in HEB-E6E7 and HEB-LTA cells. More importantly, differentiation signals can override the effects of viral oncogenes in HEB cells.
机译:1.人类胚胎脑(HEB)细胞的寿命有限,妨碍了其在神经退行性疾病治疗中的治疗用途。 2.人乳头瘤病毒16型的SV40大T抗原(LTA)或E6E7基因的稳定表达显着增加了HEB细胞的寿命,但没有诱导转化。 3.延长寿命是由抗增殖基因表达的变化触发的。我们发现LTA和E6E7-HEB细胞之间p16(INK4a),p21(WAFI),p14ARF和p53抑癌基因的表达变化,但没有p27(Kip1)的变化。 4.尽管诱导了p53 RNA,但在HEB-E6E7细胞中未检测到p53蛋白。相反,与亲代细胞相比,HEB-LTA细胞中p53蛋白增加。然而,在两种细胞系中p21的表达均降低。 5.虽然p16在HEB-E6E7细胞中减少,但其表达在HEB-LTA细胞中增加。 6.尽管有这些变化,但当细胞内cAMP水平升高时,HEB细胞系仍表现出神经元样形态分化。 7.这表明在HEB-E6E7和HEB-LTA细胞中,诱导神经元分化的机制仍然完整。更重要的是,分化信号可以超越HEB细胞中病毒致癌基因的作用。

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