Comparison of multidrug resistance gene expression levels with malignant potentials and influence of chemotherapy in urothelial cancers.
BACKGROUND
We sought to determine how often P-glycoprotein is involved in the drug-resistance of urothelial cancer, and whether MDR1 gene expression is correlated with tumor grade, invasiveness, or metastasis.


METHODS
Forty-two tumor specimens and two normal bladder mucosal samples obtained from 34 urothelial cancer patients were analyzed. Reverse-transcription and polymerase chain reaction were conducted. MDR1 mRNA levels were determined by measuring the relative ratio of the MDR1 to beta-2-microglobulin (b2 m) mRNA specific PCR products.


RESULTS
The MDR1/b2 m in two normal urothelial samples were 0.044 and 0.045. For untreated primary tumors, levels of MDR1 gene expression in 46% tumor samples were less than that of normal urothelium, while 27% showed expression levels with a MDR1/b2 m ratio more than 0.1. There was no statistical correlation between MDR1 mRNA level and tumor grade, stage, or metastatic status. There was higher MDR1 gene expression in two lymph node metastasis specimens and almost equal expressions in two more. There was no significant difference in the mean MDR1/b2 m ratio between postchemotherapy and untreated tumors. A remarkable elevation of the MDR1 mRNA level (15 times greater than prechemotherapy) was found in one tumor; mRNA levels of the multidrug resistance-associated protein (MRP) gene, glutathione S-transferase pi (GST-pi) gene or DNA topoisomerase II (topo II) gene did not increase.


CONCLUSIONS
It is still unclear whether the MDR1 gene expression in urothelial tumor cells is inducible by the current combination chemotherapy regimens. RT-PCR quantitation is useful for determining the expression level of MDR1 gene in urothelial cancer.
Kakehi
Y
Y
Department of Urology, Kyoto University, Japan.
Wu
W J
WJ
Kim
W J
WJ
Arao
S
S
Fukumoto
M
M
Yoshida
O
O
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D001613:beta 2-Microglobulin / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D005982:Glutathione Transferase; D004250:DNA Topoisomerases, Type II