Clinical Significance of Multi-Drug Resistance Associated Protein and P-Glycoprotein in Patients with Bladder Cancer

No AccessJournal of UrologyClinical Urology: Original Article1 Apr 1997Clinical Significance of Multi-Drug Resistance Associated Protein and P-Glycoprotein in Patients with Bladder Cancer Masayuki Nakagawa, Akio Emoto, Nobuyoshi Nasu, Toshikatsu Hanada, Michihiko Kuwano, Susan P.C. Cole, and Yoshio Nomura Masayuki NakagawaMasayuki Nakagawa , Akio EmotoAkio Emoto , Nobuyoshi NasuNobuyoshi Nasu , Toshikatsu HanadaToshikatsu Hanada , Michihiko KuwanoMichihiko Kuwano , Susan P.C. ColeSusan P.C. Cole , and Yoshio NomuraYoshio Nomura View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)64944-9AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The clinical significance of multi-drug resistant proteins, such as multi-drug resistance associated protein and P-glycoprotein, in terms of prognostic value was determined in patients with bladder cancer. Materials and Methods: The expression of multi-drug resistance associated protein and P-glycoprotein was investigated immunohistochemically before and after chemotherapy. The relationship between expression of these multi-drug resistant proteins and clinical outcome assessed by tumor recurrence rate, cystectomy rate and 5-year survival rate was also investigated in 33 patients with bladder cancer. Results: Before chemotherapy multi-drug resistance associated protein expression was observed in 1 of 28 patients (4%) while P-glycoprotein expression was observed in 22 of 33 (67%). Multi-drug resistance associated protein induction by chemotherapy was observed in 6 of 28 patients (21%), whereas P-glycoprotein induction was noted in 4 (14%). Multi-drug resistance associated protein in this disease is induced more frequently by high dose (more than 300 mg.) than low dose (less than 300 mg.) anthracyclines (p <0.01). Immunohistochemical analysis also revealed co-expression of multi-drug resistance associated protein and P-glycoprotein in 5 of 28 patients (18%) after chemotherapy. However, there was no significant correlation between positive P-glycoprotein expression before chemotherapy and clinical outcome. Conclusions: Multi-drug resistance associated protein as well as P-glycoprotein mediated multi-drug resistance may be induced after chemotherapy for bladder tumors. However, the presence of P-glycoprotein before chemotherapy does not predict clinical outcome in patients with bladder cancer. References 1 : Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell1986; 47: 381. Google Scholar 2 : Isolation and expression of a complementary DNA that confers multidrug resistance. Nature1986; 323: 728. Google Scholar 3 : The biochemistry of P-glycoprotein-mediated multidrug resistance. Annual Rev. Biochem.1989; 58: 137. Google Scholar 4 : Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science1992; 258: 1650. Google Scholar 5 : ABC transporters: from microorganisms to man. Ann. Rev. Cell. Biol.1992; 8: 67. Google Scholar 6 : Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs. Cancer Res.1994; 54: 357. Google Scholar 7 : Multidrug resistance-associated protein gene overexpression and reduced drug sensitivity of topoisomerase II in a human breast carcinoma MCF7 cell line selected for etoposide resistance. Cancer Res.1994; 54: 152. Google Scholar 8 : Reduced intracellular drug accumulation in the absence of P-glycoprotein (mdr1) overexpression in mitoxantrone-resistant human MCF-7 breast cancer cells. Cancer Res.1992; 52: 6175. Google Scholar 9 : Expression of the gene for multidrug-resistance-associated protein and outcome in patients with neuroblastoma. New Engl. J. Med.1996; 334: 231. Google Scholar 10 : An overview of intravesical therapy for superficial bladder tumors. J. Urol.1987; 138: 1363. Link, Google Scholar 11 : M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for advanced transitional cell carcinoma of the urothelium. J. Urol.1988; 139: 461. Link, Google Scholar 12 : Correlation between the expression of P-glycoprotein and multidrug-resistant phenotype in transitional cell carcinoma of the urinary tract. Eur. Urol.1992; 22: 158. Google Scholar 13 : Evaluation of multiple drug resistance in human bladder cancer cell lines. J. Urol.1993; 150: 505. Link, Google Scholar 14 : Expression of multidrug resistance-associated protein (MRP), MDR1 and DNA topoisomerase II in human multidrug-resistant bladder cancer cell lines. Brit. J. Cancer1995; 71: 907. Google Scholar 15 : Reversal by a dihydropyridine derivative of non-P-glycoprotein-mediated multidrug resistance in etoposide-resistant human prostatic cancer cell line. J. Urol.1995; 154: 1210. Abstract, Google Scholar 16 : P-glycoprotein expression in bladder cancer. J. Urol.1994; 151: 43. Link, Google Scholar 17 : Expression of the multidrug resistance-associated protein (MRP) gene in human cancers. Clin. Canc. Res.1995; 1: 1301. Google Scholar 18 : Sequential coexpression of the multidrug resistance genes MRP and mdr1 and their products in VP-16(etoposide)-selected H69 small cell lung cancer cells. Cancer Res.1995; 55: 459. Google Scholar 19 : Mutation rates and mechanisms of resistance to etoposide determined from fluctuation analysis. J. Natl. Cancer Inst.1994; 86: 1152. Google Scholar 20 : Heat shock and arsenite increase expression of the multidrug resistance (MDR1) gene in human renal carcinoma cells. J. Biol. Chem.1990; 265: 221. Google Scholar 21 : Regulation of the multidrug resistance gene in regenerating rat liver. Cell Growth Differ.1990; 1: 57. Google Scholar 22 : The direct activation of human multidrug resistance gene (MDR1) by anticancer agents. Biochem. Biophys. Res. Comm.1989; 165: 1415. Google Scholar 23 : Enhanced expression of the human multidrug resistance 1 gene in response to UV light irradiation. Cell Growth Differ.1993; 4: 147. Google Scholar 24 : P-glycoprotein expression in primary and metastatic transitional cell carcinoma of the bladder. Ann. Oncol.1994; 5: 835. Google Scholar 25 : Absence of immunohistochemical metallothionein staining in bladder tumor specimens predicts response to neoadjuvant cisplatin, methotrexate and vinblastine chemotherapy. J. Urol.1994; 152: 2272. Link, Google Scholar 26 : DNA ploidy and P-glycoprotein expression as predictive factors of response to neoadjuvant chemotherapy for invasive bladder cancer. Urology1994; 43: 787. Google Scholar 27 : Expression of MDR-1 gene in transitional cell carcinoma and its correlation with chemotherapy response. J. Urol.1996; 156: 271. Link, Google Scholar 28 : Increased mdr1 gene transcript levels in high-grade carcinoma of the bladder determined by quantitative PCR-based assay. Brit. J. Cancer1994; 69: 680. Google Scholar 29 : Alterations in expression of the multidrug resistance-associated protein (MRP) gene in high-grade transitional cell carcinoma of the bladder. Brit. J. Cancer1996; 73: 659. Google Scholar 30 Abe, T., Mori, T., Wakabayashi, Y., Nakagawa, M., Akiyama, S., Deeley, R. G., Cole, S. P. C., Koike, K., Kohno, K., Kuwano, M. and Hori, S.: Unpublished data. Google Scholar 31 : Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors: consensus recommendations. Cancer Res.1996; 56: 3010. Google Scholar From the Department of Urology, Oita Medical University, Oita, and Department of Biochemistry, Kyushu University School of Medicine, Fukuoka, Japan, and Cancer Research Laboratories, Queen's University, Kingston, Canada© 1997 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byLewin J, Lwaleed B, Cooper A and Birch B (2018) The Direct Effect of Nuclear Pores on Nuclear Chemotherapeutic Concentration in Multidrug Resistant Bladder Cancer: The Nuclear Sparing PhenomenonJournal of Urology, VOL. 177, NO. 4, (1526-1530), Online publication date: 1-Apr-2007.Speers A, Lwaleed B, Featherstone J and Cooper A (2018) Multidrug Resistance in a Urothelial Cancer Cell Line After 3, 1-Hour Exposures to Mitomycin CJournal of Urology, VOL. 178, NO. 5, (2171-2175), Online publication date: 1-Nov-2007.DIESTRA J, CONDOM E, DEL MURO X, SCHEFFER G, PÉREZ J, ZURITA A, MUÑOZ-SEGUÍ J, VIGUÉS F, SCHEPER R, CAPELLÁ G, GERMÀ-LLUCH J and IZQUIERDO M (2018) Expression of Multidrug Resistance Proteins P-Glycoprotein, Multidrug Resistance Protein 1, Breast Cancer Resistance Protein and Lung Resistance Related Protein in Locally Advanced Bladder Cancer Treated With Neoadjuvant Chemotherapy: Biological and Clinical ImplicationsJournal of Urology, VOL. 170, NO. 4 Part 1, (1383-1387), Online publication date: 1-Oct-2003.SOLOMON L, JENNINGS A, SHARPE P, COOPER A and BIRCH B (2018) INTRAVESICAL CHEMOTHERAPY WITH GAMMA LINOLENIC ACID BECOMES A REALISTIC PROSPECT IN SERUM-FREE APPLICATIONS: IN VITRO CYTOTOXICITY AND SYSTEMIC ABSORPTION STUDIESJournal of Urology, VOL. 160, NO. 6 Part 1, (2280-2283), Online publication date: 1-Dec-1998.STEIN J, GROSSFELD G, GINSBERG D, ESRIG D, FREEMAN J, FIGUEROA A, SKINNER D and COTE R (2018) PROGNOSTIC MARKERS IN BLADDER CANCER: A CONTEMPORARY REVIEW OF THE LITERATUREJournal of Urology, VOL. 160, NO. 3 Part 1, (645-659), Online publication date: 1-Sep-1998. Volume 157Issue 4April 1997Page: 1260-1265 Advertisement Copyright & Permissions© 1997 by American Urological Association, Inc.MetricsAuthor Information Masayuki Nakagawa More articles by this author Akio Emoto More articles by this author Nobuyoshi Nasu More articles by this author Toshikatsu Hanada More articles by this author Michihiko Kuwano More articles by this author Susan P.C. Cole More articles by this author Yoshio Nomura More articles by this author Expand All Advertisement PDF downloadLoading ...