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Multidrug resistance-associated protein (MRP) gene expression in human lung cancer
F Narasaki1, I Matsuo, N Ikuno
1Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Abstract:
Multidrug resistance-associated protein (MRP) is a 190 kD transmembrane protein and a potentially important drug-transporter protein in human cancers. While the MRP gene is expressed in normal cells and tissues, the expression in solid tumors is not sufficiently determined. MRP and mdr1 mRNA expressions were examined in normal lung parenchyma and in tumor tissues from six small cell lung cancer (SCLC) patients who had received preoperative chemotherapy and eleven nonsmall cell lung cancer (NSCLC) patients. The reverse transcriptase polymerase chain reaction was used. Normal lung tissues and all SCLCs expressed abundant levels of MRP mRNA, while the NSCLCs expressed a wide range of levels from low to high. Most tumor tissues coexpressed both MRP and mdr1, but the levels of mdrl expression was low except in two SCLCs and one NSCLC. MRP is more likely than mdr1 to be one of the clinical multidrug resistance mechanisms found in lung cancer.
Insights
Multidrug resistance-associated protein (MRP) is a key drug transporter in lung cancer. This study found higher MRP mRNA expression in lung tumors than mdr1, suggesting MRP is a primary driver of multidrug resistance in lung cancer.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Multidrug resistance-associated protein (MRP) is a transmembrane transporter implicated in human cancers.
- While MRP gene expression is known in normal tissues, its role in solid tumors, particularly lung cancer, requires further elucidation.
Purpose of the Study:
- To investigate and compare the mRNA expression levels of MRP and mdr1 in normal lung tissue, small cell lung cancer (SCLC), and nonsmall cell lung cancer (NSCLC).
- To determine the potential contribution of MRP and mdr1 to multidrug resistance in lung cancer.
Main Methods:
- Utilized reverse transcriptase polymerase chain reaction (RT-PCR) to quantify MRP and mdr1 mRNA expression.
- Analyzed tissue samples from normal lung parenchyma, SCLC patients (post-chemotherapy), and NSCLC patients.
Main Results:
- Abundant MRP mRNA expression was detected in normal lung tissues and all SCLC samples.
- NSCLC samples exhibited a broad range of MRP mRNA expression, from low to high.
- Coexpression of MRP and mdr1 was common in tumor tissues, though mdr1 expression levels were generally low, except in specific SCLC and NSCLC cases.
Conclusions:
- MRP is more frequently and abundantly expressed in lung cancer tissues compared to mdr1.
- MRP is likely a significant contributor to clinical multidrug resistance mechanisms in lung cancer.