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    Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12117-22. Epub 2007 Jul 11.

    Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancer.

    Rottenberg S, Nygren AO, Pajic M, van Leeuwen FW, van der Heijden I, van de Wetering K, Liu X, de Visser KE, Gilhuijs KG, van Tellingen O, Schouten JP, Jonkers J, Borst P.

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    Division of Molecular Biology and Center of Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.

    Abstract

    We have studied in vivo responses of "spontaneous" Brca1- and p53-deficient mammary tumors arising in conditional mouse mutants to treatment with doxorubicin, docetaxel, or cisplatin. Like human tumors, the response of individual mouse tumors varies, but eventually they all become resistant to the maximum tolerable dose of doxorubicin or docetaxel. The tumors also respond well to cisplatin but do not become resistant, even after multiple treatments in which tumors appear to regrow from a small fraction of surviving cells. Classical biochemical resistance mechanisms, such as up-regulated drug transporters, appear to be responsible for doxorubicin resistance, rather than alterations in drug-damage effector pathways. Our results underline the promise of these mouse tumors for the study of tumor-initiating cells and of drug therapy of human cancer.

    PMID:
    17626183
    [PubMed - indexed for MEDLINE]
    PMCID: PMC1914039
    Free PMC Article

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