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Expression of the MRP and MDR1 multidrug resistance genes in small cell lung cancer
B G Campling1, L C Young, K A Baer
1Cancer Research Laboratory, Department of Oncology, Queen's University, Kingston, Ontario, K7L 3N6 Canada.
Abstract:
Acquired multidrug resistance is a major obstacle to a cure for small cell lung cancer (SCLC). Overexpression of the MDR1 gene occurs infrequently in multidrug-resistant SCLC cell lines. The multidrug resistance protein (MRP) can confer multidrug resistance, but its role in clinically acquired drug resistance is unknown. The purpose of this study was to measure expression of MRP and MDR1 mRNA in cell lines and clinical samples from SCLC patients and to correlate the results with drug sensitivity profiles. Twenty-three SCLC cell lines and 10 tumor samples from SCLC patients were examined. Samples expressing MRP and MDR1 were identified by reverse transcription-PCR, and levels of MRP mRNA in the cell lines were measured by quantitative reverse transcription-PCR. One of 23 cell lines (4%) expressed MDR1 mRNA, whereas MRP expression was detected in 19 of 23 cell lines (83%). There was a significant correlation between doxorubicin resistance and MRP expression levels (r = 0.422; P = 0.045). Of the 10 clinical samples, 3 expressed only MRP, 2 expressed only MDR1, and 4 expressed both drug resistance genes. In summary, MRP is frequently expressed in clinical samples and cell lines from SCLC patients, and the levels correlate with doxorubicin resistance in unselected SCLC cell lines. Expression of MDR1 can be detected in clinical samples of SCLC but is rarely found in cell lines from drug-resistant patients. These multidrug resistance proteins may contribute to the multifactorial problem of clinically acquired drug resistance in SCLC.
Insights
Multidrug resistance protein (MRP) is frequently found in small cell lung cancer (SCLC) cell lines and tumors, correlating with doxorubicin resistance. MDR1 gene expression is rare in SCLC cell lines but present in clinical samples.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Acquired multidrug resistance (MDR) is a significant challenge in treating small cell lung cancer (SCLC).
- While MDR1 gene overexpression is uncommon in resistant SCLC cell lines, the role of multidrug resistance-associated protein (MRP) in clinical drug resistance remains unclear.
Purpose of the Study:
- To quantify MRP and MDR1 mRNA expression in SCLC cell lines and clinical samples.
- To investigate the correlation between MRP/MDR1 expression and drug sensitivity profiles in SCLC.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect MRP and MDR1 expression.
- Quantitative RT-PCR measured MRP mRNA levels in 23 SCLC cell lines and 10 clinical SCLC tumor samples.
Main Results:
- MRP mRNA was detected in 83% (19/23) of SCLC cell lines, while MDR1 mRNA was found in only 4% (1/23).
- A significant correlation was observed between higher MRP expression levels and doxorubicin resistance (r = 0.422; P = 0.045).
- In clinical samples, 3/10 expressed only MRP, 2/10 expressed only MDR1, and 4/10 expressed both.
Conclusions:
- MRP is frequently expressed in SCLC cell lines and clinical samples, contributing to doxorubicin resistance.
- MDR1 expression is less common in SCLC cell lines but detectable in clinical samples, suggesting a complex role in SCLC drug resistance.