Loss of p53 in CRaf-induced transgenic lung adenoma leads to tumor acceleration and phenotypic switch

Lev M. Fedorov, Thomas Papadopoulos, Oleg Y. Tyrsin, Thomas Twardzik, Rudolf Götz, Ulf R. Rapp

    Research output: Contribution to journalArticle

    23 Scopus citations

    Abstract

    One of the most frequent malignancies in humans is lung adenocarcinoma. To develop novel diagnostic and therapeutic approaches for the management of this disease, animal models are required. We have used transgenic mice with lung-targeted expression of the CRaf kinase to evaluate genes altered frequently in human lung adenocarcinoma for their effect on tumor progression. Here we report that loss of p53 dramatically accelerates tumor development and induces a phenotypic switch in the target cell from cuboid to a nonciliated columnar morphology. Coexpression of lung epithelial cell markers surfactant protein C and Clara cell antigen suggests that tumor cell dedifferentiation could be involved in this process. The effect of p53 is specific, because loss of one of its target genes, p21CIFI/WAFI, did not have this effect on cell phenotype although tumor latency was also reduced significantly. Neither loss of p53 nor p21 stimulated acquisition of the metastasis program beyond the stage of bronchiolar extension. This mouse model for pulmonary adenoma and adenocarcinoma should be very helpful for a better understanding of pathogenesis and treatment of this most deadly human cancer.

    Original languageEnglish (US)
    Pages (from-to)2268-2277
    Number of pages10
    JournalCancer Research
    Volume63
    Issue number9
    StatePublished - May 1 2003

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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  • Cite this

    Fedorov, L. M., Papadopoulos, T., Tyrsin, O. Y., Twardzik, T., Götz, R., & Rapp, U. R. (2003). Loss of p53 in CRaf-induced transgenic lung adenoma leads to tumor acceleration and phenotypic switch. Cancer Research, 63(9), 2268-2277.