Expression of the multidrug resistance-associated protein (MRP) gene in urothelial carcinomas

✍ Scribed by Hiroyuki Kubo; Tomoyuki Sumizawa; Keisuke Koga; Kenryu Nishiyama; Yuji Takebayashi; Yutaka Chuman; Tatsuhiko Furukawa; Shin-ichi Akiyama; Yoshitada Ohi

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 667 KB
• Volume: 69
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19961220)69:6<488::aid-ijc13>3.0.co;2-y

✦ Synopsis

The intrinsic or acquired resistance of urothelial cancer to chemotherapy is one major obstacle to successful treatment. Generally, the expression level of P-glycoprotein in urothelial cancer is low, so we accordingly investigated the expression of multidrug resistance-associated protein (MRP). We examined the expression of M R P mRNA by means of slot-blotting samples of I I renal pelvic and/or ureteral tumors, 33 bladder tumors, one lung metastasis from a ureter tumor, 7 non-cancerous urothelia from patients with transitional-cell carcinoma (TCC) and one urothelium from a patient with renal-cell carcinoma (RCC). We also estimated, by Southern blotting, whether or not the M R P gene was amplified in clinical specimens that overexpressed M R P mRNA. MRP was detected immunohistochemically using a polyclonal antibody against MRP. In all, 5 of I I renal pelvic and/or ureter tumors (45.5940). I7 of 33 bladder tumors (51.5Y0) and 4 of 7 non-cancerous urothelia of TCC patients (57. I Yo) expressed more than 2-fold the M R P mRNA levels of drug-sensitive human KB cells. There was no significant difference in the M R P mRNA level between primary and recurrent tumors. Low-grade urothelial carcinomas (GI and G2 TCCs) expressed significantly higher levels of M R P mRNA than the high-grade G3 TCC. The M R P gene was not amplified in urothelial carcinomas, irrespective of their expression levels of M R P mRNA. lmmunohistochemically, MRP was located mainly on the plasma membrane, but also detected on the cytoplasm of cancer cells. MRP may be one mechanism responsible for intrinsic drug resistance in low-grade urothelial cancer.