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Detection of MDM2-proto-oncogene in paraffin embedded human bronchial epithelium

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Abstract

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.

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References

  • Barak Y, Juven T, Haffner R, Oren M (1993) mdm2 expression is induced by wild type p53 activity. EMBO J 12:461–468

    PubMed  Google Scholar 

  • Fakharzadeh SS, Trusko SP, George DL (1991) Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J 10:1565–1569

    PubMed  Google Scholar 

  • Finlay CA (1992) Normal and malignant growth control by p53. In: Benz CC, Liu ET (eds) Oncogenes and tumor suppressor genes in human malignancies. Kluwer Academic, Boston, pp. 327–344

    Google Scholar 

  • Fromentel CC de, Soussi T (1992) TP53 tumor suppressor gene: a model for investigating human mutagenesis. Genes Chromosomes Cancer 4:1–15

    PubMed  Google Scholar 

  • Leach FS, Tokino T, Meltzer P, Burrel M, Oliner JD, Smith S, Hill DE, Sidransky D, Kinzler K, Vogelstein B (1993) p53 mutation and MDM2 amplification in human soft tissue Sarcomas. Cancer Res 53: 2231–2234

    PubMed  Google Scholar 

  • Levine AJ (1992) The p53 tumour suppressor gene and product. Cancer Surv 12:59–79

    PubMed  Google Scholar 

  • Momand J, Zambetti GP, Olson DC, George D, Levine AJ (1992) The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69:1237–1245

    PubMed  Google Scholar 

  • Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B (1992) Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358:80–83

    PubMed  Google Scholar 

  • Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW, Vogelstein B (1993) Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature 362:857–860

    PubMed  Google Scholar 

  • Reifenberger G, Liu L, Ichimura K, Schmidt EE, Collins VP (1993) Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. Cancer Res 53:2736–2739

    PubMed  Google Scholar 

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Wiethege, T., Voss, B. & Müller, K.M. Detection of MDM2-proto-oncogene in paraffin embedded human bronchial epithelium. J Cancer Res Clin Oncol 120, 252–255 (1994). https://doi.org/10.1007/BF01372566

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  • DOI: https://doi.org/10.1007/BF01372566

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