Reid R L, Lindholm P F, Mireskandari A, Dittmer J, Brady J N
Laboratory of Molecular Virology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Oncogene. 1993 Nov;8(11):3029-36.
Adult T-cell leukemia/lymphoma is an aggressive malignancy associated with infection by the human T-lymphotropic virus type-I (HTLV-I). We now demonstrate that p53 expression is elevated in the HTLV-I-transformed T-lymphocyte lines C81, MT-2, MT-4 and HUT 102. In pulse-chase experiments, the p53 protein demonstrated a prolonged half-life of 2 to 8 h in HTLV-I-transformed cells compared with 0.5 to 1.0 h for wild-type p53 in primary human and murine fibroblasts, or human peripheral blood lymphocytes. In cell lines C81 and HUT 102, which exhibited the longest p53 protein half-life, the wild-type-related PAb1620 epitope was detected at reduced levels. The PAb240 mutant-related p53 epitope was not detected in any of the transformed cell lines. By direct sequence analysis of RT-PCR products, the entire p53 cDNA coding sequence was determined to be wild-type in all four cell lines. Stabilization of wild-type p53 may represent its functional inactivation and contribute to lymphocyte transformation by HTLV-I.
成人T细胞白血病/淋巴瘤是一种侵袭性恶性肿瘤，与人T淋巴细胞白血病病毒I型（HTLV-I）感染相关。我们现在证明，在HTLV-I转化的T淋巴细胞系C81、MT-2、MT-4和HUT 102中，p53表达升高。在脉冲追踪实验中，与原代人及鼠成纤维细胞或人外周血淋巴细胞中野生型p53的半衰期0.5至1.0小时相比，p53蛋白在HTLV-I转化细胞中的半衰期延长至2至8小时。在p53蛋白半衰期最长的细胞系C81和HUT 102中，野生型相关的PAb1620表位检测水平降低。在任何转化细胞系中均未检测到PAb240突变体相关的p53表位。通过对RT-PCR产物进行直接序列分析，确定所有四个细胞系中整个p53 cDNA编码序列均为野生型。野生型p53的稳定化可能代表其功能失活，并有助于HTLV-I介导的淋巴细胞转化。
