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British Journal of Cancer logoLink to British Journal of Cancer
. 1997;75(2):208–212. doi: 10.1038/bjc.1997.35

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

M Fillpits 1, R W Suchomel 1, G Dekan 1, W Stiglbauer 1, K Haider 1, D Depisch 1, R Pirker 1
PMCID: PMC2063277  PMID: 9010028

Abstract

To determine the clinical significance of MRP in patients with colorectal carcinomas, we have studied the expression of the MRP gene by reverse transcription-polymerase chain reaction (RT-PCR) (n = 105) and by immunohistochemistry (n = 30). MRP mRNA expression was observed in 92 (88%) tumour specimens. Positive MRP staining with monoclonal antibodies QCRL-1 and QCRL-3 was detected in all samples studied with strong staining in seven (23%) and weak staining in 23 (77%) specimens. Strong MRP staining in these samples did not appear to be related to the age and sex of the patients, localization of the primary tumour, histological grade, tumour size, lymph node metastasis, distant metastasis and tumour stage. Strong MRP staining was not associated with MDR1 RNA or P-glycoprotein (P-gp) expression. Kaplan-Meier curves revealed that overall survival of patients with strong MRP-staining tumours was similar to the survival of patients with weak-staining tumours. These data indicate that the MRP gene is expressed in primary colorectal carcinomas but is neither related to known prognostic factors nor a prognostic factor by itself.

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Selected References

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  1. Barrand M. A., Heppell-Parton A. C., Wright K. A., Rabbitts P. H., Twentyman P. R. A 190-kilodalton protein overexpressed in non-P-glycoprotein-containing multidrug-resistant cells and its relationship to the MRP gene. J Natl Cancer Inst. 1994 Jan 19;86(2):110–117. doi: 10.1093/jnci/86.2.110. [DOI] [PubMed] [Google Scholar]
  2. Beck W. T. Unknotting the complexities of multidrug resistance: the involvement of DNA topoisomerases in drug action and resistance. J Natl Cancer Inst. 1989 Nov 15;81(22):1683–1685. doi: 10.1093/jnci/81.22.1683. [DOI] [PubMed] [Google Scholar]
  3. Bordow S. B., Haber M., Madafiglio J., Cheung B., Marshall G. M., Norris M. D. Expression of the multidrug resistance-associated protein (MRP) gene correlates with amplification and overexpression of the N-myc oncogene in childhood neuroblastoma. Cancer Res. 1994 Oct 1;54(19):5036–5040. [PubMed] [Google Scholar]
  4. Brock I., Hipfner D. R., Nielsen B. S., Jensen P. B., Deeley R. G., Cole S. P., Sehested M. 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 Feb 1;55(3):459–462. [PubMed] [Google Scholar]
  5. Chin K. V., Ueda K., Pastan I., Gottesman M. M. Modulation of activity of the promoter of the human MDR1 gene by Ras and p53. Science. 1992 Jan 24;255(5043):459–462. doi: 10.1126/science.1346476. [DOI] [PubMed] [Google Scholar]
  6. Cole S. P., Bhardwaj G., Gerlach J. H., Mackie J. E., Grant C. E., Almquist K. C., Stewart A. J., Kurz E. U., Duncan A. M., Deeley R. G. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 1992 Dec 4;258(5088):1650–1654. doi: 10.1126/science.1360704. [DOI] [PubMed] [Google Scholar]
  7. Cole S. P., Sparks K. E., Fraser K., Loe D. W., Grant C. E., Wilson G. M., Deeley R. G. Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. Cancer Res. 1994 Nov 15;54(22):5902–5910. [PubMed] [Google Scholar]
  8. De Angelis P., Stokke T., Smedshammer L., Lothe R. A., Lehne G., Chen Y., Clausen O. P. P-glycoprotein is not expressed in a majority of colorectal carcinomas and is not regulated by mutant p53 in vivo. Br J Cancer. 1995 Aug;72(2):307–311. doi: 10.1038/bjc.1995.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Filipits M., Suchomel R. W., Dekan G., Haider K., Valdimarsson G., Depisch D., Pirker R. MRP and MDR1 gene expression in primary breast carcinomas. Clin Cancer Res. 1996 Jul;2(7):1231–1237. [PubMed] [Google Scholar]
  10. Goldstein L. J., Galski H., Fojo A., Willingham M., Lai S. L., Gazdar A., Pirker R., Green A., Crist W., Brodeur G. M. Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst. 1989 Jan 18;81(2):116–124. doi: 10.1093/jnci/81.2.116. [DOI] [PubMed] [Google Scholar]
  11. Gottesman M. M., Pastan I. The multidrug transporter, a double-edged sword. J Biol Chem. 1988 Sep 5;263(25):12163–12166. [PubMed] [Google Scholar]
  12. Grant C. E., Valdimarsson G., Hipfner D. R., Almquist K. C., Cole S. P., Deeley R. G. Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs. Cancer Res. 1994 Jan 15;54(2):357–361. [PubMed] [Google Scholar]
  13. Hipfner D. R., Gauldie S. D., Deeley R. G., Cole S. P. Detection of the M(r) 190,000 multidrug resistance protein, MRP, with monoclonal antibodies. Cancer Res. 1994 Nov 15;54(22):5788–5792. [PubMed] [Google Scholar]
  14. Kruh G. D., Chan A., Myers K., Gaughan K., Miki T., Aaronson S. A. Expression complementary DNA library transfer establishes mrp as a multidrug resistance gene. Cancer Res. 1994 Apr 1;54(7):1649–1652. [PubMed] [Google Scholar]
  15. Lehnert M. Reversal of P-glycoprotein-associated multidrug resistance: the challenge continues. Eur J Cancer. 1993;29A(4):636–638. doi: 10.1016/s0959-8049(05)80169-8. [DOI] [PubMed] [Google Scholar]
  16. Loe D. W., Almquist K. C., Deeley R. G., Cole S. P. Multidrug resistance protein (MRP)-mediated transport of leukotriene C4 and chemotherapeutic agents in membrane vesicles. Demonstration of glutathione-dependent vincristine transport. J Biol Chem. 1996 Apr 19;271(16):9675–9682. doi: 10.1074/jbc.271.16.9675. [DOI] [PubMed] [Google Scholar]
  17. Mayer A., Takimoto M., Fritz E., Schellander G., Kofler K., Ludwig H. The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and mdr gene expression in colorectal cancer. Cancer. 1993 Apr 15;71(8):2454–2460. doi: 10.1002/1097-0142(19930415)71:8<2454::aid-cncr2820710805>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  18. Milroy R. A randomised clinical study of verapamil in addition to combination chemotherapy in small cell lung cancer. West of Scotland Lung Cancer Research Group, and the Aberdeen Oncology Group. Br J Cancer. 1993 Oct;68(4):813–818. doi: 10.1038/bjc.1993.433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Noonan K. E., Beck C., Holzmayer T. A., Chin J. E., Wunder J. S., Andrulis I. L., Gazdar A. F., Willman C. L., Griffith B., Von Hoff D. D. Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7160–7164. doi: 10.1073/pnas.87.18.7160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nooter K., Westerman A. M., Flens M. J., Zaman G. J., Scheper R. J., van Wingerden K. E., Burger H., Oostrum R., Boersma T., Sonneveld P. Expression of the multidrug resistance-associated protein (MRP) gene in human cancers. Clin Cancer Res. 1995 Nov;1(11):1301–1310. [PubMed] [Google Scholar]
  21. Norris M. D., Bordow S. B., Marshall G. M., Haber P. S., Cohn S. L., Haber M. Expression of the gene for multidrug-resistance-associated protein and outcome in patients with neuroblastoma. N Engl J Med. 1996 Jan 25;334(4):231–238. doi: 10.1056/NEJM199601253340405. [DOI] [PubMed] [Google Scholar]
  22. Pastan I., Gottesman M. Multiple-drug resistance in human cancer. N Engl J Med. 1987 May 28;316(22):1388–1393. doi: 10.1056/NEJM198705283162207. [DOI] [PubMed] [Google Scholar]
  23. Pirker R., Keilhauer G., Raschack M., Lechner C., Ludwig H. Reversal of multi-drug resistance in human KB cell lines by structural analogs of verapamil. Int J Cancer. 1990 May 15;45(5):916–919. doi: 10.1002/ijc.2910450523. [DOI] [PubMed] [Google Scholar]
  24. Pirker R., Wallner J., Geissler K., Linkesch W., Haas O. A., Bettelheim P., Hopfner M., Scherrer R., Valent P., Havelec L. MDR1 gene expression and treatment outcome in acute myeloid leukemia. J Natl Cancer Inst. 1991 May 15;83(10):708–712. doi: 10.1093/jnci/83.10.708. [DOI] [PubMed] [Google Scholar]
  25. Pirker R., Wallner J., Gsur A., Götzl M., Zöchbauer S., Scheithauer W., Depisch D. MDR1 gene expression in primary colorectal carcinomas. Br J Cancer. 1993 Oct;68(4):691–694. doi: 10.1038/bjc.1993.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Roepe P. D. The role of the MDR protein in altered drug translocation across tumor cell membranes. Biochim Biophys Acta. 1995 Dec 20;1241(3):385–405. doi: 10.1016/0304-4157(95)00013-5. [DOI] [PubMed] [Google Scholar]
  27. Roepe P. D., Wei L. Y., Cruz J., Carlson D. Lower electrical membrane potential and altered pHi homeostasis in multidrug-resistant (MDR) cells: further characterization of a series of MDR cell lines expressing different levels of P-glycoprotein. Biochemistry. 1993 Oct 19;32(41):11042–11056. doi: 10.1021/bi00092a014. [DOI] [PubMed] [Google Scholar]
  28. Simon S. M., Schindler M. Cell biological mechanisms of multidrug resistance in tumors. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3497–3504. doi: 10.1073/pnas.91.9.3497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sinicrope F. A., Hart J., Brasitus T. A., Michelassi F., Lee J. J., Safa A. R. Relationship of P-glycoprotein and carcinoembryonic antigen expression in human colon carcinoma to local invasion, DNA ploidy, and disease relapse. Cancer. 1994 Dec 1;74(11):2908–2917. doi: 10.1002/1097-0142(19941201)74:11<2908::aid-cncr2820741104>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  30. Thomas G. A., Barrand M. A., Stewart S., Rabbitts P. H., Williams E. D., Twentyman P. R. Expression of the multidrug resistance-associated protein (MRP) gene in human lung tumours and normal tissue as determined by in situ hybridisation. Eur J Cancer. 1994;30A(11):1705–1709. doi: 10.1016/0959-8049(94)00290-l. [DOI] [PubMed] [Google Scholar]
  31. Twentyman P. R. MDR1 (P-glycoprotein) gene expression--implications for resistance modifier trials. J Natl Cancer Inst. 1992 Oct 7;84(19):1458–1460. doi: 10.1093/jnci/84.19.1458. [DOI] [PubMed] [Google Scholar]
  32. Zaman G. J., Versantvoort C. H., Smit J. J., Eijdems E. W., de Haas M., Smith A. J., Broxterman H. J., Mulder N. H., de Vries E. G., Baas F. Analysis of the expression of MRP, the gene for a new putative transmembrane drug transporter, in human multidrug resistant lung cancer cell lines. Cancer Res. 1993 Apr 15;53(8):1747–1750. [PubMed] [Google Scholar]

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