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Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
Published on: May 11, 2016
Expression of drug resistance-related genes in head and neck squamous cell carcinomas and normal mucosa
1Department of Otorhinolaryngology, Hiroshima University Faculty of Medicine. hirata@mcai.med.hiroshima-u.ac.jp
Abstract:
We examined the expression levels of mRNA for multidrug resistance 1 (MDR1), multidrug resistance-associated protein (MRP), human canalicular multispecific organic anion transporter (cMOAT), lung resistance-related protein (LRP), topoisomerase IIalpha, beta (Topo IIalpha, beta) and topoisomerase I (Topo I) genes in human head and neck squamous cell carcinoma (HNSCC) specimens and mucosa (HNM) specimens, to elucidate their roles in relation to the biological characteristics and drug resistance in vivo. Fifty-eight samples (45 head and neck carcinomas and 13 head and neck mucosa) obtained during surgical resection or biopsy from 38 patients were analyzed using the quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. MDR1, MRP, LRP, Topo IIalpha, Topo IIbeta, and Topo I gene transcripts were detected in all the samples tested, but cMOAT mRNA was not detected in them. Comparisons of the expression levels in HNSCC with those in HNM showed that the Topo IIalpha gene expression level was higher in HNSCC than in HNM (P=0.0298). Moreover, the Topo IIalpha mRNA level was significantly higher in metastatic lymph node samples of HNSCC than in HNM samples (P=0.0205). There were no significant differences in the six genes' expression levels between samples exposed to platinum drugs and those not exposed to platinum drugs. These results suggest that it may be effective in anticancer therapy to use topoisomerase-targetting drugs against HNSCC, especially metastatic neck tumors, and that the expression of these genes in HNSCC is not associated with platinum drug exposure.
Insights
This study found higher Topoisomerase IIalpha gene expression in head and neck squamous cell carcinoma (HNSCC), particularly in metastatic tumors. This suggests topoisomerase-targeting drugs may be effective for HNSCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Head and neck squamous cell carcinoma (HNSCC) is a significant health concern.
- Understanding the molecular mechanisms of drug resistance in HNSCC is crucial for effective treatment.
- Several genes, including multidrug resistance (MDR) genes and topoisomerases, are implicated in cancer drug resistance.
Purpose of the Study:
- To investigate the expression levels of key drug resistance genes in HNSCC.
- To correlate gene expression with biological characteristics and in vivo drug resistance in HNSCC.
- To evaluate the potential of targeting specific genes in HNSCC therapy.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze gene expression.
- Fifty-eight human samples (45 HNSCC, 13 normal mucosa) were analyzed.
- Expression levels of MDR1, MRP, cMOAT, LRP, Topo IIalpha, Topo IIbeta, and Topo I genes were quantified.
Main Results:
- MDR1, MRP, LRP, Topo IIalpha, Topo IIbeta, and Topo I mRNA were detected in all samples; cMOAT mRNA was not detected.
- Topo IIalpha gene expression was significantly higher in HNSCC compared to normal head and neck mucosa (P=0.0298).
- Topo IIalpha mRNA levels were also significantly elevated in metastatic lymph node samples of HNSCC (P=0.0205).
- No significant differences in gene expression were observed between platinum drug-exposed and non-exposed samples.
Conclusions:
- Elevated Topo IIalpha expression in HNSCC, especially in metastatic tumors, suggests its potential as a therapeutic target.
- Topoisomerase-targeting drugs may be effective for treating HNSCC, particularly advanced cases.
- The expression of the studied genes in HNSCC does not appear to be associated with prior platinum drug exposure.

