Measurement of multidrug-resistance messenger RNA in urogenital cancers; elevated expression in renal cell carcinoma is associated with intrinsic drug resistance.
We measured the levels of messenger RNA of the human multidrug-resistance gene (MDR1) in 25 urogenital tumors before chemotherapy. Many of the renal cell carcinomas continued to express MDR1 gene at high levels, reflecting the increased expression of MDR1 RNA in normal kidneys. In other urogenital tumors, the MDR1 RNA levels were low reflecting low MDR1 RNA levels in normal bladder, prostate and testis. For comparative purposes, we performed in vitro chemosensitivity testing on many tumor samples using soft agar culture techniques. Vinblastine sensitivity in vitro inversely correlated with MDR1 RNA levels (p less than 0.01). Moreover, mean sensitivity of seven renal cell carcinomas to vinblastin was significantly lower than that of the other seven cancers (p less than 0.05). As for doxorubicin, mean sensitivity of six renal cell carcinomas was lower than the others (p less than 0.1). These results suggest that the high MDR1 RNA levels in renal cell carcinomas are associated with intrinsic multidrug-resistance.
Kakehi
Y
Y
Department of Urology, Kyoto University Faculty of Medicine, Japan.
Kanamaru
H
H
Yoshida
O
O
Ohkubo
H
H
Nakanishi
S
S
Gottesman
M M
MM
Pastan
I
I
D002292:Carcinoma, Renal Cell / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D005786:Gene Expression Regulation; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D014565:Urogenital Neoplasms / Q000235:genetics*
D012333:RNA, Messenger