Adenovirus-mediated transfer of the p53 gene produces rapid and generalized death of human glioma cells via apoptosis.
Adenovirus-mediated transfer of the p53 gene produces rapid and generalized death of human glioma cells via apoptosis.
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发表时间：
1996-02
期刊：
影响因子：
11.2
通讯作者：
C. Gomez-Manzano;J. Fueyo;A. Kyritsis;P. Steck;J. A. Roth;Timothy J. McDonnell;K. Steck;Victor A. Le
中科院分区：
文献类型：
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作者：
C. Gomez-Manzano;J. Fueyo;A. Kyritsis;P. Steck;J. A. Roth;Timothy J. McDonnell;K. Steck;Victor A. Le
野生型p53参与细胞周期控制和转化抑制的几个方面，诱导细胞凋亡或细胞周期进展中的G1阻滞。使用含有野生型p53 cDNA的重组腺病毒，新表达的野生型p53蛋白的生物学效应在6个人胶质瘤细胞系中进行了研究。三种细胞系（U-251 MG、U-373 MG和A-172）表达内源性突变型p53，而其他三种细胞系（U-87 MG、EFC-2和D54 MG）表达野生型p53。正常的p53编码蛋白的突变体细胞系的恢复诱导细胞凋亡的形态学研究，使用核染色，电子显微镜和流式细胞仪测定进行评估。然而，在野生型p53细胞系中，野生型p53的过表达并不导致细胞凋亡，但抑制细胞增殖，而急剧和修改的肿瘤表型。差异效应提示胶质瘤肿瘤发生的两种途径和一种可能的治疗策略。
Wild-type p53 is involved in several aspects of cell cycle control and suppression of transformation, inducing either apoptosis or G1 block in cell cycle progression. Using a recombinant adenovirus containing the wild-type p53 cDNA, the biological effects of the newly expressed wild-type p53 protein were examined in six human glioma cell lines. Three cell lines (U-251 MG, U-373 MG, and A-172) expressed endogenous mutant p53, and the other three (U-87 MG, EFC-2, and D54 MG) expressed wild-type p53. The restoration of normal p53-encoded protein in the mutant cell lines induced apoptosis as assessed by morphological studies using nuclear staining, electron microscopy, and flow cytometric assays. In wild-type p53 cell lines, however, the overexpression of wild-type p53 did not result in apoptosis but inhibited cellular proliferation rather drastically and modified the neoplastic phenotype. Differential effects suggest two pathways for glioma oncogenesis and a possible therapeutic strategy.