Wiethege T, Voss B, Müller K M
Professional Associations' Research Institute for Occupational Medicine-BGFA, Bochum, Germany.
J Cancer Res Clin Oncol. 1994;120(4):252-5. doi: 10.1007/BF01372566.
Recently a new proto-oncogene, the murine double-minute 2 (MDM2), has been described. MDM2 becomes oncogenic due to amplification and overexpression. Among other proto-oncogenes MDM2 becomes interesting since MDM2 protein can associate with both mutant and wild type p53 tumor suppressor gene products and thus inhibit p53-mediated transactivation of other genes. Loss of p53 tumor suppressor function is the most frequently observed alteration in human tumors. Immunohistochemical studies investigating the quantity of MDM2 protein in human sarcomas revealed an overexpression in 30% of the specimens. Here we describe the successful use of a monoclonal antibody (IF2) for the detection of MDM2 protein in paraffin-embedded tissue from human lung biopsies. 18 out of 44 specimens (41%), predominantly mucosal epithelial and glandular epithelial cells, stained positive for MDM2. No significant difference was observed between non-cancerogenic cells adjacent to tumor cells and those specimens without any tumor cells but altered by inflammatory processes. In general, the staining pattern was restricted not to the nuclei, but to selected subnuclear compartments, probably representing the golgi apparatus or the endoplasmatic reticulum. Our data support the hypothesis that in addition to its nuclear function of forming a complex with p53, MDM2 may also be secreted and thus have a transcellular effect.
最近，一种新的原癌基因——小鼠双微体2（MDM2）已被报道。MDM2因扩增和过表达而具有致癌性。在其他原癌基因中，MDM2变得引人关注，因为MDM2蛋白可与突变型和野生型p53肿瘤抑制基因产物结合，从而抑制p53介导的其他基因的反式激活。p53肿瘤抑制功能的丧失是人类肿瘤中最常见的改变。对人类肉瘤中MDM2蛋白数量进行研究的免疫组织化学研究显示，30%的标本中有过表达。在此，我们描述了一种单克隆抗体（IF2）在检测人肺活检石蜡包埋组织中MDM2蛋白方面的成功应用。44个标本中有18个（41%），主要是黏膜上皮细胞和腺上皮细胞，MDM2染色呈阳性。在肿瘤细胞旁的非致癌细胞与那些无任何肿瘤细胞但因炎症过程而改变的标本之间未观察到显著差异。一般来说，染色模式不仅限于细胞核，还局限于选定的核内亚区室，可能代表高尔基体或内质网。我们的数据支持这样一种假说，即除了其与p53形成复合物的核功能外，MDM2也可能被分泌，从而具有跨细胞效应。
