Quantitative analysis of multidrug resistance gene expression in human osteosarcomas.
We evaluated the MDR1 expression levels in 77 osteosarcomas and investigated whether MDR1 mRNA expression in osteosarcomas varies with location within the tumour, following chemotherapy, or after metastasis. We modified the semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) assay to determine accurately the levels of MDR1 mRNA expression in clinical specimens. We show that specimens collected from multiple locations in six tumours revealed very little variation in MDR1 expression suggesting that the levels of MDR1 in these tumours do not vary greatly with location within the tumour mass. In a comparison of pre and post-chemotherapy specimens it was found that MDR1 levels did not change appreciably following chemotherapy in 16 of 20 cases. In addition, in eight of ten specimens obtained before and after metastasis, the amount of MDR1 mRNA was found to remain relatively constant despite metastatic spread. Thus, many osteosarcomas exhibited intrinsic expression of MDR1 mRNA before multidrug regimens which invariably included doxorubicin and, in most cases, MDR1 expression was not induced following chemotherapeutic treatment. Our results suggest that some osteosarcoma patients may have primary tumours which are resistant to doxorubicin. These individuals may benefit from different chemotherapeutic regimens, e.g. the addition of MDR reversal agents.
Lee
P D
PD
Department of Molecular and Cellular Pathology, University of Toronto, Canada.
Noble-Topham
S E
SE
Bell
R S
RS
Andrulis
I L
IL
D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics*; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*
D012333:RNA, Messenger