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[Relationship between p 53 gene mutation and MDR 1 gene expression in surgically resected non-small cell lung cancer]
A Takahashi1, K Kohri, T Ohnuki
1First Department of Medicine, Tokyo Women's Medical University, Japan.
Abstract:
The resistance of tumor cells to chemotherapeutic drugs is a major obstacle to successful cancer chemotherapy. Expression of the MDR 1 gene, which encodes for a transmembrane efflux pump (P-glycoprotein), leads to decreased intracellular accumulation and resistance to a variety of anticancer drugs. Recently, one mutant p 53 form was shown to stimulate the MDR 1 gene promoter in vitro, whereas wild-type p 53 repressed this activity. We examined the relationship between p 53 gene mutation and MDR 1 gene expression in specimens from non-small cell lung cancer patients. Tumor samples were obtained from 21 patients during surgery. Mutations of exon 5 through exon 8 of the p 53 gene were detected by the polymerase chain reaction single strand conformation polymorphism method. MDR 1 expression was semi-quantified by the reverse transcriptase polymerase chain reaction method. We identified p 53 gene mutation in samples from 7 patients. MDR 1 gene expression was observed in samples from 20 patients. The expressivity of the MDR 1 gene tended to be higher in patients with adenocarcinoma. No significant relationship between p 53 mutation and MDR 1 expressivity was observed in our study.
Insights
Tumor cells resist chemotherapy partly due to the MDR1 gene. This study found no direct link between p53 gene mutations and MDR1 gene expression in non-small cell lung cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Context:
- Tumor cell resistance to chemotherapy is a significant challenge in cancer treatment.
- The MDR1 gene, encoding P-glycoprotein, contributes to multidrug resistance by effluxing anticancer drugs.
- Previous in vitro studies suggested a role for mutant p53 in upregulating MDR1 expression.
Purpose:
- To investigate the relationship between p53 gene mutations and MDR1 gene expression in non-small cell lung cancer (NSCLC).
- To determine if p53 mutations correlate with altered MDR1 expression levels in NSCLC patient specimens.
Summary:
- This study analyzed p53 gene mutations (exons 5-8) and MDR1 gene expression in 21 NSCLC tumor samples.
- p53 mutations were found in 7 patients, while MDR1 expression was detected in 20 patients.
- No significant association was observed between p53 gene mutation status and MDR1 gene expressivity, although MDR1 expression trended higher in adenocarcinoma subtypes.
Impact:
- The findings suggest that p53 mutation status may not be a reliable predictor of MDR1 expression in NSCLC.
- Further research is needed to elucidate the complex mechanisms underlying MDR1 regulation in lung cancer.
- This study contributes to understanding drug resistance mechanisms in NSCLC, potentially informing future therapeutic strategies.