Schlott T, Reimer S, Jahns A, Ohlenbusch A, Ruschenburg I, Nagel H, Droese M
Department of Pathology, Georg-August-University, Goettingen, Germany.
J Pathol. 1997 May;182(1):54-61. doi: 10.1002/(SICI)1096-9896(199705)182:1<54::AID-PATH815>3.0.CO;2-I.
This study investigates the human oncoprotein MDM2, which interferes with regulation of cell division and apoptosis. Fifteen mixed-type follicular non-Hodgkin's lymphomas, ten leukaemias, two hepatocellular carcinomas, one osteosarcoma, and ten normal cell lines (fibroblasts, osteoblasts, mesothelium, peripheral lymphocytes) were tested for MDM2 expression and MDM2 gene mutation by reverse transcriptase-polymerase chain reaction (RT-PCR), immunocytochemistry, and nucleotide sequence analysis. Two follicular lymphomas, three leukaemias, both hepatocellular carcinomas, and the osteosarcoma sample showed transcription of the activated MDM2 gene. These samples lacked amplified MDM2 genes and carried mis-sense, non-sense and frame-shift mutations in a zinc finger region of MDM2, altering the amino acid sequence or causing premature termination of transcription. The mis-sense mutations were found in tumour cells that showed significant accumulation of MDM2 and lack of nuclear p53. Non-sense mutations and frame-shift mutations were found in tumours lacking MDM2 proteins. The mutations may affect the biological properties of MDM2 proteins.
本研究调查了人类癌蛋白MDM2，它干扰细胞分裂和凋亡的调控。通过逆转录聚合酶链反应（RT-PCR）、免疫细胞化学和核苷酸序列分析，对15例混合型滤泡性非霍奇金淋巴瘤、10例白血病、2例肝细胞癌、1例骨肉瘤以及10种正常细胞系（成纤维细胞、成骨细胞、间皮、外周淋巴细胞）进行了MDM2表达和MDM2基因突变检测。2例滤泡性淋巴瘤、3例白血病、2例肝细胞癌以及骨肉瘤样本均显示出活化的MDM2基因转录。这些样本中MDM2基因未扩增，且在MDM2的一个锌指区域存在错义、无义及移码突变，改变了氨基酸序列或导致转录提前终止。错义突变见于MDM2显著蓄积且缺乏核p53的肿瘤细胞中。无义突变和移码突变见于缺乏MDM2蛋白的肿瘤中。这些突变可能会影响MDM2蛋白的生物学特性。
