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Absence of structural alterations of the multidrug resistance genes in transitional cell carcinoma


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.

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  1. 1.

    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

  2. 2.

    Bell DR, Trent JM, Willard HF, Riordan JR, Ling V (1987) Chromosomal location of human P-glycoprotein gene sequences. Cancer Genet Cytogenet 25:141

  3. 3.

    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

  4. 4.

    Feinberg A, Vogelstein B (1984) Addendum. A technique for radiolabeling DNA restriction fragments to high specific activity. Anal Biochem 137:266

  5. 5.

    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

  6. 6.

    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

  7. 7.

    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

  8. 8.

    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

  9. 9.

    Ling V, Karner N, Sudo T, Siminovich L, Riordan J (1983) Multidrug-resistance phenotypein Chinese hamster ovary cells. Cancer Treat Rep 67:869

  10. 10.

    Montie JE, Straffon R, Stewart BH (1984) Radical cystectomy without irradiation therapy for carcinoma of the bladder. J Urol 131:477

  11. 11.

    Pastan I, Gottesman MM (1987) Multidrug resistance in human cancer. N Engl J Med 316:1388

  12. 12.

    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

  13. 13.

    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

  14. 14.

    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

  15. 15.

    Sandberg AA (1986) Chromosome changes in bladder cancer: clinical other correlations. Cancer Genet Cytogenet 19:163

  16. 16.

    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

  17. 17.

    Schnipper L (1986) Clinical implications of tumor-cell heterogeneity. N Engl J Med 314:1423

  18. 18.

    Scotto KW, Biedler JL, Melera PW (1986) Amplification expression of genes associated with multidrug resistance in mammalian cells. Science 232:751

  19. 19.

    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

  20. 20.

    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

  21. 21.

    Skipper H, Schabel F (1984) Tumor stem cell heterogeneity: implications with respect to classification of cancers by chemotherapeutic effect. Cancer Treat Rep 68:43

  22. 22.

    Southern E (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503

  23. 23.

    Steffen D, Weinberg R (1978) The integrated genome of murine leukemia virus. Cell 15:1003

  24. 24.

    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

  25. 25.

    Whitmore WF G (1980) Integrated irradiation cystectomy for bladder cancer. Br J Urol 52:1

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Author information

Correspondence to E. A. Klein or R. S. K. Chaganti.

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

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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

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Key words

  • Multidrug resistance genes
  • Transitional cell carcinoma
  • Gene amplification