EXPRESSION OF THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP) GENE IN HUMAN CANCERS(1)

We determined the expression of a newly recognized drug resistance gen e, the multidrug resistance-associated protein (MRP) gene, [Cole et al ., Science (Washington DC), 258: 1650-1654, 1992], in normal human tis sues and in >370 human tumor biopsies using a quantitative RNase prote ction assay and immunohistochemistry. MRP mRNA appeared to be ubiquito usly expressed at low levels in all normal tissues, including peripher al blood, the endocrine glands (adrenal and thyroid), striated muscle, the lymphoreticular system (spleen and tonsil), the digestive tract ( salivary gland, esophagus, liver, gall bladder, pancreas, and colon), the respiratory tract (lung), and the urogenital tract (kidney, bladde r, testis, and ovary). The human cancers analyzed could be divided int o three groups with regard to MRP expression. Group 1 consists of tumo rs that often exhibit high to very high MRP mRNA levels (e.g., chronic lymphocytic leukemia). Group 2 comprises the tumors that often exhibi t low, but occasionally exhibit high MRP mRNA expression (e.g., esopha gus squamous cell carcinoma, nonsmall cell lung cancer, and acute myel ocytic leukemia). Group 3 comprises the tumors with predominantly low levels of MRP mRNA, comparable to the levels found in normal tissues ( e.g., other hematological malignancies, soft tissue sarcomas, melanoma , and cancers of the prostate, breast, kidney, bladder, testis, ovary, and colon). Using the MRP-specific mAbs MRPr1 and MRPm6, we confirmed the elevated MRP mRNA levels in tumor tissues by immunohistochemistry . We conclude that hyperexpression of MRP is observed in several human cancers, and that additional studies are needed to assess the clinica l relevance of MRP.