Gomez-Manzano C, Fueyo J, Kyritsis A P, Steck P A, Roth J A, McDonnell T J, Steck K D, Levin V A, Yung W K
Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Cancer Res. 1996 Feb 15;56(4):694-9.
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.
野生型p53参与细胞周期调控和转化抑制的多个方面，可诱导细胞凋亡或使细胞周期进程阻滞于G1期。利用携带野生型p53 cDNA的重组腺病毒，在六种人胶质瘤细胞系中检测了新表达的野生型p53蛋白的生物学效应。三种细胞系（U-251 MG、U-373 MG和A-172）表达内源性突变型p53，另外三种（U-87 MG、EFC-2和D54 MG）表达野生型p53。通过核染色、电子显微镜和流式细胞术分析等形态学研究评估，突变细胞系中正常p53编码蛋白的恢复诱导了细胞凋亡。然而，在野生型p53细胞系中，野生型p53的过表达并未导致细胞凋亡，而是显著抑制了细胞增殖并改变了肿瘤表型。不同的效应提示了胶质瘤发生的两条途径以及一种可能的治疗策略。
