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  • Title: Point mutations in the mdr1 promoter of human osteosarcomas are associated with in vitro responsiveness to multidrug resistance relevant drugs.
    Author: Stein U, Walther W, Wunderlich V.
    Journal: Eur J Cancer; 1994; 30A(10):1541-5. PubMed ID: 7833115.
    Abstract:
    Among human sarcomas, osteosarcomas usually display high intrinsic mdr1 expression while malignant fibrous histiocytomas (MFH) do not. A comparative polymerase chain reaction (PCR)-based sequence analysis of the mdr1 promoter revealed point mutations in seven out of nine osteosarcomas at nucleotides +103 (2 cases T-->C) and +137 (5 cases G-->T). No changes were seen in eight MFHs. When COS cells transfected with CAT constructs containing the T-->C chloramphenicol acetyltransferase mutant mdr1 promoters were treated with vincristine or doxorubicin, expression of the CAT gene was enhanced to a higher extent than with constructs containing wild-type or G-->T-mutant mdr1 promoters. We suggest that there is a correlation between the type of mdr1 promoter mutation and responsiveness to MDR relevant drugs.
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