Ungar S, Van de Meeren A, Tammilehto L, Linnainmaa K, Mattson K, Gerwin B I
Laboratory of Human Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA.
Br J Cancer. 1996 Nov;74(10):1534-40. doi: 10.1038/bjc.1996.585.
Prior analysis of 20 human mesothelioma cell lines for p53 status revealed only two mutations and one p53 null cell line, although p53 expression was detected in most cell lines. In addition, mRNA and protein expression of the retinoblastoma gene product in human mesothelioma cell lines is similar to normal controls. We have tested for p53 induction after exposure to ionising radiation and demonstrate this induction and, to a lesser extent, p21(WAF1) induction, in both normal mesothelial cells and p53-positive mesothelioma cell lines. We postulated that high levels of MDM2 might alter p53 and retinoblastoma tumour-suppressor function in mesothelioma. However, Southern blot analysis for mdm2 indicated that no amplification had occurred in 18 mesothelioma cell lines tested. Steady-state mRNA and protein levels also did not indicate overexpression. These results indicate that high levels of MDM2 are not responsible for inactivating the functions of wild-type p53 or the retinoblastoma gene product during the pathogenesis of malignant mesothelioma.
先前对20个人类间皮瘤细胞系的p53状态进行分析发现，尽管在大多数细胞系中检测到了p53表达，但仅发现两个突变和一个p53缺失细胞系。此外，人类间皮瘤细胞系中视网膜母细胞瘤基因产物的mRNA和蛋白质表达与正常对照相似。我们检测了电离辐射暴露后p53的诱导情况，并证明在正常间皮细胞和p53阳性间皮瘤细胞系中均有这种诱导，以及在较小程度上p21（WAF1）的诱导。我们推测，高水平的MDM2可能会改变间皮瘤中p53和视网膜母细胞瘤肿瘤抑制功能。然而，对mdm2的Southern印迹分析表明，在测试的18个间皮瘤细胞系中未发生扩增。稳态mRNA和蛋白质水平也未表明存在过表达。这些结果表明，在恶性间皮瘤的发病机制中，高水平的MDM2并非导致野生型p53或视网膜母细胞瘤基因产物功能失活的原因。
