Expression of multidrug resistance-related genes in oral squamous cell carcinomas.
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.
Cho
Y S
YS
Department 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
Kim
M J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015870:Gene Expression; D019450:Genes, MDR / Q000235:genetics*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
D004250:DNA Topoisomerases, Type II; D005982:Glutathione Transferase; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger