Summary
Tumor DNA from 27 patients with treated or untreated transitional cell carcinomas of the urinary tract was screened for genomic alterations of the multidrug resistance genes in order to determine whether structural changes of these genes are important in primary urothelial tumors. None of the tumors showed evidence of amplification or rearrangements of either mdr1 or mdr2. The lack of amplification or rearrangements observed in these tumors suggests that structural alterations of the mdr1 and mdr2 genes are not important mediators of drug resistance in TCC.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bell DR, Gerlach JH, Kartner N, Buick RN, Ling V (1985) Detection of P-glycoprotein in ovarian cancer: a molecular marker associated with multidrug resistance. J Clin Oncol 3:311
Bell DR, Trent JM, Willard HF, Riordan JR, Ling V (1987) Chromosomal location of human P-glycoprotein gene sequences. Cancer Genet Cytogenet 25:141
Choi K, Chen C-j, Kriegler M, Roninson IB (1988) An altered pattern of cross-resistance in multidrug resistant human cells results from spontaneous mutations in the mdrl (P-glycoprotein) gene. Cell 53:519
Feinberg A, Vogelstein B (1984) Addendum. A technique for radiolabeling DNA restriction fragments to high specific activity. Anal Biochem 137:266
Fojo A, Ueda K, Slamon D, Poplack D, Gottesman M, Pastan I (1987) Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci USA 84:265
Fojo AT, Ding-Wu S, Mickley LA, Pastan IG, Gottesman MM (1987) Intrinsic drug resistance in human kidney cancer is associated with expression of a human multidrug-resistance gene. J Clin Oncol 5:1922
Gros P, Croop J, Roninson IB, Varshavsky A, Housman DE (1986) Isolation and characterization of DNA sequences amplified in multidrug-resistant hamster cells. Proc Natl Acad Sci USA 83:337
Kakehi Y, Kanamaru H, Yoshida O, Ohkubo H, Nakanishi S, Gottesman MM, Pastan I (1988) Measurement of multidrug resistance messenger RNA in urogenital cancers; elevated expression in renal cell carcinoma is associated with intrinsic drug resistance. J Urol 139:862
Ling V, Karner N, Sudo T, Siminovich L, Riordan J (1983) Multidrug-resistance phenotypein Chinese hamster ovary cells. Cancer Treat Rep 67:869
Montie JE, Straffon R, Stewart BH (1984) Radical cystectomy without irradiation therapy for carcinoma of the bladder. J Urol 131:477
Pastan I, Gottesman MM (1987) Multidrug resistance in human cancer. N Engl J Med 316:1388
Riordan JR, Dewhars K, Kartner N, Alon N, Trent J, Ling V (1985) Amplification of P-glycoprotein in multidrug-resistant mammalian cell lines. Nature 316:817
Roninson IB, Abelson HT, Housman DE, Howell N, Varshavsky A (1984) Amplification of specific DNA sequences correlates with multidrug resistance in Chinese hamster cells. Nature 309:626
Roninson IB, Chin JE, Choi K, Gros P, Housman DE, Fojo A, Shen D-w, Gottesman MM, Pastan I (1986) Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells. Proc Natl Acad Sci USA 83:4538
Sandberg AA (1986) Chromosome changes in bladder cancer: clinical other correlations. Cancer Genet Cytogenet 19:163
Scher H, Yagoda A, Herr H, Sternberg C, Bosl G, Morse M, Sogani P, Watson R, Dershaw DD, Reuter V, Geller N, Holler P, Vaughan ED, Whitmore WF, Fair WR (1988) Neoadjuvant MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin): effect on the primary bladder lesion. J Urol 139:470
Schnipper L (1986) Clinical implications of tumor-cell heterogeneity. N Engl J Med 314:1423
Scotto KW, Biedler JL, Melera PW (1986) Amplification expression of genes associated with multidrug resistance in mammalian cells. Science 232:751
Shen D-w, Fojo A, Chin JE, Roninson IB, Richert N, Pastan I, Gottesman MM (1986) Human multidrug-resistant cell lines: increased mdr1 expression can precede gene amplification. Science 232:643
Skinner DG, Lieskovsky G (1984) Contemporary cystectomy with pelvic lymph node dissection compared to preoperative radiation therapy pluscystectomy in the management of invasive bladder cancer. J Urol 131:1069
Skipper H, Schabel F (1984) Tumor stem cell heterogeneity: implications with respect to classification of cancers by chemotherapeutic effect. Cancer Treat Rep 68:43
Southern E (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503
Steffen D, Weinberg R (1978) The integrated genome of murine leukemia virus. Cell 15:1003
Sternberg C, Yagoda A, Scher HI, Watson R, Ahmed T, Weiselberg L, Geller N, Holler P, Herr H, Sogani P, Morse M, Whitmore WF (1985) Preliminary results of M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) for transitional cell carcinoma of the urothelium. J Urol 133:403
Whitmore WF G (1980) Integrated irradiation cystectomy for bladder cancer. Br J Urol 52:1
Author information
Authors and Affiliations
Additional information
Supported in part by grant CA-34775 from the National Institutes of Health and by a grant from the Heckscher Foundation for Children
Dr. Klein is a fellow of the American Cancer Society
Rights and permissions
About this article
Cite this article
Klein, E.A., Allen, G., Fair, W.R. et al. Absence of structural alterations of the multidrug resistance genes in transitional cell carcinoma. Urol. Res. 18, 281–286 (1990). https://doi.org/10.1007/BF00294774
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00294774