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Expression of multidrug resistance-related genes in oral squamous cell carcinomas
1Department of Oral and Maxillofacial Surgery, College of Medicine and Medical Research Institute, Chungbuk National University, #62 Gaeshin-Dong, Heungdeok-Gu. Cheongju, Chungbuk, 361-240, South Korea. yscho@med.chungbuk.ac.kr
Abstract:
To characterize the multidrug resistance (MDR) phenotype in human oral squamous cell carcinomas (OSCCs), the expression levels of four MDR-related genes (multidrug resistance, mdr1; multidrug resistance-associated protein, MRP; glutathione S-transferase-pi, GST-pi; and DNA topoisomerase II, topoII) were analyzed in OSCCs. Fifty-two OSCC tissues and 22 normal oral mucosal tissues were involved in this study. The expression of each gene was analyzed with a reverse-transcription polymerase chain reaction (RT-PCR) method using beta(2)m microglobulin (beta(2)m) mRNA as an endogenous control. The mean values of mdr1, MRP, GST-pi, and topoII gene expression relative to the beta(2)m gene in OSCC tissues were 0.37, 0.75, 0.66, and 1.11; those of normal oral mucosa were 0.40, 0.27, 0.62, and 0.91, respectively. The averaged expression levels of the MRP and topoII gene in OSCC tissues were higher than those of normal oral mucosas (P=0.001 and P=0.02, respectively). The expression levels of four MDR-related genes in OSCCs were not related with the degree of histologic cell differentiation, tumor stage, primary or recurred tumor, or the presence or absence of chemotherapy. Linear regression analysis showed a correlation between the expression levels of MRP and GST-pi in normal oral mucosas (r=0.596, P=0.003) and in OSCCs (r=0.287, P=0.039). The results suggest that MRP expression is activated during the tumorigenesis of OSCCs and that this may play a role in de novo drug resistance in OSCCs. These results should provide further insight into the complex role postulated for MDR-related genes in chemotherapy, carcinogenesis and tumor progression.
Insights
Multidrug resistance (MDR)-related genes MRP and topoisomerase II are upregulated in oral squamous cell carcinomas (OSCCs), suggesting a role in de novo drug resistance. This activation during OSCC tumorigenesis offers insights into MDR gene function.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multidrug resistance (MDR) is a significant challenge in treating oral squamous cell carcinomas (OSCCs).
- Understanding the expression of MDR-related genes is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate the expression levels of four key MDR-related genes: multidrug resistance (mdr1), multidrug resistance-associated protein (MRP), glutathione S-transferase-pi (GST-pi), and DNA topoisomerase II (topoII) in OSCC.
- To correlate gene expression with clinical parameters and explore potential roles in drug resistance and tumorigenesis.
Main Methods:
- Analysis of mdr1, MRP, GST-pi, and topoII gene expression in 52 OSCC tissues and 22 normal oral mucosal tissues.
- Reverse-transcription polymerase chain reaction (RT-PCR) was used with beta(2)m microglobulin (beta(2)m) mRNA as an endogenous control.
- Statistical analysis including linear regression was performed to assess correlations and significance.
Main Results:
- Averaged expression levels of MRP and topoII genes were significantly higher in OSCC tissues compared to normal oral mucosa (P=0.001 and P=0.02, respectively).
- No significant correlation was found between the expression of these four genes and clinicopathological features like differentiation, tumor stage, or prior chemotherapy.
- A positive correlation was observed between MRP and GST-pi expression in both normal oral mucosa and OSCC tissues.
Conclusions:
- MRP gene expression appears to be activated during OSCC tumorigenesis, potentially contributing to de novo drug resistance.
- The findings suggest that MRP plays a role in the development of drug resistance in OSCC.
- These results enhance the understanding of MDR-related genes in OSCC carcinogenesis, progression, and chemotherapy response.