Multidrug resistance-1 gene expression does not increase during tumor progression in the MGH-OGS murine osteosarcoma...

In addition to its possible role in drug resistance, expression of the multidrug resistance-1 gene may also be associated with a more malignant phenotype and tumor progression. This study evaluated its expression during tumor progression in the MGH-OGS transplantable murine osteosarcoma tumor model. Three variables of tumor progression were analyzed: tumor size, local recurrence, and metastasis. With a highly sensitive reverse transcription-polymerase chain reaction method, mRNA levels of multidrug resistance-1 were compared in primary tumors of different sizes. In addition, the levels were compared in primary, locally recurrent, and metastatic tumors isolated from individual mice. No significant difference was found in the levels of expression with increasing primary tumor size. In addition, the levels in primary, locally recurrent, and metastatic tumors were not significantly different. Our results indicate that--at least in the MGH-OGS tumor model, which is analogous to the majority of spontaneously occurring human osteosarcomas in that it has low levels of multidrug resistance-1/P-glycoprotein and is sensitive to doxorubicin--there is no evidence of upregulation of multidrug resistance-1 expression during tumor progression.