Skip to main content
Log in

The Role of Half-Transporters in Multidrug Resistance

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

ATP-binding cassette proteins comprise a superfamily of transporter proteins, a subset of which have been implicated in multidrug resistance. Although P-glycoprotein was described over 15 years ago, the recent expansion in the number of transporters identified has prompted renewed interest in the role of drug transporters in clinical drug resistance. These newly identified transporters include additional members of the MRP family, ABC2, and a new half-transporter, MXR/BCRP/ABCP1. This half-transporter confers high levels of resistance to mitoxantrone, anthracyclines, and the camptothecins SN-38 and topotecan. At 72 kDa, MXR localizes to the plasma membrane in cells which highly overexpress the protein either through gene amplification or though gene rearrangement. Future studies will be aimed at identifying an inhibitor, and attempting to translate recognition of this new transporter into a target for anticancer treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  • Abele, R., and Tampe, R. (1999). Biochim. Biophys. Acta 1461, 405–419.

    Google Scholar 

  • Allen, J. D., Brinkhuis, R. F., Wijnholds, J., and Schinkel, A. H. (1999). Cancer Res. 59, 4237–4241.

    Google Scholar 

  • Allikmets, R., Gerrard, B., Hutchinson, A., and Dean, M. (1996). Hum. Mol. Genet. 5, 1649–1655.

    Google Scholar 

  • Allikmets, R., Schriml, L. M., Hutchinson, A., Romano-Spica, V., and Dean, M. (1998). Cancer Res. 58, 5337–5339.

    Google Scholar 

  • Beck, W. T., Grogan, T. M., Willman, C. L., Cordon-Cardo, C., Parham, D. M., Kuttesch, J. F., Andreeff, M., Bates, S. E., Berard, C. W., Boyett, J. M., Brophy, N. A., Broxterman, H. J., Chan, H. S. L., Dalton, W. S., Dietel, M., Fojo, A. T., Gascoyne, R. D., Head, D., Houghton, P. J., Srivastava, D. K., Lehnert, M., Leith, C. P., Paietta, E., Pavelic, Z. P., Rimsza, L., Roninson, I. B., Sikic, B. I., Twentyman, P. R., Warnke, R., and Weinstein, R. (1996). Cancer Res. 56, 3010–3020.

    Google Scholar 

  • Borst, P., Evers, R., Kool, M., and Wijnholds, J. (1999). Biochim. Biophys. Acta 1461, 347–357.

    Google Scholar 

  • Brangi, M., Litman, T., Ciotti, M., Nishiyama, K., Kohlhagen, G., Takimoto, C., Robey, R., Pommier, Y., Fojo, T., and Bates, S. E. (1999). Cancer Res. 59, 5938–5946.

    Google Scholar 

  • Childs, S., Yeh, R. L., Hui, D., and Ling, V. (1998). Cancer Res. 58, 4160–4167.

    Google Scholar 

  • Cole, S. P. C., Bhardwaj, G., Gerlach, J. H., Mackie, J. E., Grant, C. E., Almquist, K. C., Stewart, A. J., Kurz, E. U., Duncan, A. M., and Deeley, R. G. (1992). Science 258, 1650–1654.

    Google Scholar 

  • Dalton, W. S., Cress, A. E., Alberts, D. S., and Trent, J. M. (1988). Cancer Res. 48, 1882–1888.

    Google Scholar 

  • de Bruin, M., Miyake, K., Litman, T., Robey, R., and Bates, S. E. (1999). Cancer Lett. 146, 117–126.

    Google Scholar 

  • Dietel, M., Arps, H., Lage, H., and Niendorf, A. (1990). Cancer Res. 50, 6100–6106.

    Google Scholar 

  • Doyle, L. A., Yang, W., Abruzzo, L. E., Krogmann, T., Gao, Y., Rishi, A. K., and Ross, D. D. (1998a). Proc. Am. Assoc. Cancer Res. 39A.

  • Doyle, L. A., Yang, W., Abruzzo, L. V., Krogmann, T., Gao, Y., Rishi, A. K., and Ross, D. D. (1998b). Proc. Natl. Acad. Sci. U.S.A. 95, 15665–15670.

    Google Scholar 

  • Ewart, G. D., and Howells, A. J. (1998). In Methods in Enzymology (Ambudkar, S., and Gottesman, M. M., eds.), Academic Press, San Diego, pp. 213–224.

    Google Scholar 

  • Hazlehurst, L. A., Foley, N. E., Gleason-Guzman, M. C., Hacker, M. P., Cress, A. E., Greenberger, L. W., De Jong, M. C., and Dalton, W. S. (1999). Cancer Res. 59, 1021–1028.

    Google Scholar 

  • Higgins, C. F. (1992). Annu. Rev. Cell Biol. 8, 67–113.

    Google Scholar 

  • Hipfner, D. R., Deeley, R. G., and Cole, S. P. (1999). Biochem. Biophys. Acta 1461, 359–376.

    Google Scholar 

  • Jedlitschky, G., Leier, I., Buchholz, U., Barnouin, K., Kurz, G., and Keppler, D. (1996). Cancer Res. 56, 988–994.

    Google Scholar 

  • Klein, I., Sarkadi, B., and Varadi, A. (1999). Biochim. Biophys. Acta 1461, 237–262.

    Google Scholar 

  • Knutsen, T., Rao, V. K., Ried, T., Mickley, L., Schneider, E., Miyake, K., Ghadimi, B. M., Padilla-Nash, H., Pack, S., Greenberger, L., Cowan, K., Dean, M., Fojo, T., and Bates, S. (2000). Genes Chromosomes Cancer 27, 110–116.

    Google Scholar 

  • Kool, M., de Haas, M., Scheffer, G. L., Scheper, R. J., van Eijk, M. J., Juijn, J. A., Baas, F., and Borst, P. (1997). Cancer Res. 57, 3537–3547.

    Google Scholar 

  • Kool, M., van der Linden, M., de Haas, M., Scheffer, G. L., De Vree, J. M., Smith, A. J., Jansen, G., Peters, G. J., Ponne, N., Scheper, R. J., Elferink, R. P., Baas, F., and Borst, P. (1999). Proc. Natl. Acad. Sci. U.S.A. 96, 6914–6919.

    Google Scholar 

  • Laing, N. M., Belinsky, M. G., Kruh, G. D., Bell, D. W., Boyd, J. T., Barone, L., Testa, J. R., and Tew, K. D. (1998). Cancer Res. 58, 1332–1337.

    Google Scholar 

  • Lee, J. S., Paull, K., Alvarez, M., Hose, C., Monks, A., Grever, M., Fojo, A. T., and Bates, S. E. (1994). Mol. Pharmacol. 46, 627–638.

    Google Scholar 

  • Lee, J. S., Scala, S., Matsumoto, Y., Dickstein, B., Robey, R., Zhan, Z., Altenberg, G., and Bates, S. E. (1997). J. Cell. Biochem. 65, 513–526.

    Google Scholar 

  • Ling, V. (1997). Cancer Chemother. Pharmacol. 40(Suppl)., S3–S8.

    Google Scholar 

  • Litman, T., Brangi, M., Hudson, E., Fetsch, P., Abati, A., Ross, D. D., Miyake, K., Resau, J. H., and Bates, S. E. (2000). J. Cell Sci. 113, 2011–2021.

    Google Scholar 

  • Liu, L. X., Janvier, K., Berteaux-Lecellier, V., Cartier, N., Benarous, R., and Aubourg, P. (1999). J. Biol. Chem. 274, 32738–32743.

    Google Scholar 

  • Ma, J., Maliepaard, M., Nooter, K., Loos, W. J., Kolker, H. J., Verweij, J., Stoter, G., and Schellens, J. H. (1998). Br. J. Cancer 77, 1645–1652.

    Google Scholar 

  • Malayeri, R., Filipits, M., Suchomel, R. W., Zochbauer, S., Lechner, K., and Pirker, R. (1996). Leuk. Lymphoma 23, 451–458.

    Google Scholar 

  • Maliepaard, M., van Gastelen, M. A., de Jong, L. A., Pluim, D., van Waardenburg, R. C., Ruevekamp-Helmers, M. C., Floot, B. G., and Schellens, J. H. (1999). Cancer Res. 59, 4559–4563.

    Google Scholar 

  • Miyake, K., Mickley, L., Litman, T., Zhan, Z., Robey, R., Cristensen, B., Brangi, M., Greenberger, L., Dean, M., Fojo, T., and Bates, S. E. (1999). Cancer Res. 59, 8–13.

    Google Scholar 

  • Nakagawa, M., Schneider, E., Dixon, K. H., Horton, J., Kelley, K., Morrow, C., and Cowan, K. H. (1992). Cancer Res. 52, 6175–6181.

    Google Scholar 

  • Rabindran, S. K., He, H., Singh, M., Brown, E., Collins, K. I., Annable, T., and Greenberger, L. M. (1998). Cancer Res. 58, 5850–5858.

    Google Scholar 

  • Rabindran, S. K., Ross, D. D., Doyle, L. A., Yang, W., and Greenberger, L. M. (2000). Cancer Res. 60, 47–50.

    Google Scholar 

  • Rocchi, E., Khodjakov, A., Volk, E. L., Yang, C. H., Litman, T., Bates, S. E., and Schneider, E. (2000). Biochem. Biophys. Res. Commun. 271, 42–46.

    Google Scholar 

  • Ross, D. D. (2000). Leukemia 14, 467–473.

    Google Scholar 

  • Ross, D. D., Yang, W., Abruzzo, L. V., Dalton, W. S., Schneider, E., Lage, H., Dietel, M., Greenberger, L., Cole, S. P., and Doyle, L. A. (1999). J. Natl., Cancer Inst. 91, 429–433.

    Google Scholar 

  • Sandor, V., Fojo, T., and Bates, S. E. (1998). Drug Resist Updates 1, 190–200.

    Google Scholar 

  • Scheffer, G. L., Maliepaard, M., Pijnenborg, A. C. L. M., van Gastelen, M. A., de Jong, M. C., Schroeijers, A. B., van der Kolk, D. M., Allen, J. D., Ross, D. D., van der Valk, P., Dalton W. S., Schellens, J. H. M., and Scheper, R. J. (2000). Cancer Res. 60, 2589–2593.

    Google Scholar 

  • Strautnieks, S. S., Bull, L. N., Knisely, A. S., Kocoshis, S. A., Dahl, N., Arnell, H., Sokal, E., Dahan, K., Childs, S., Ling, V., Tanner, M. S., Kagalwalla, A. F., Nemeth, A., Pawlowska, J., Baker, A., Mieli-Vergani, G., Freimer, N. B., Gardiner, R. M., and Thompson, R. J. (1998). Nat. Genet. 20, 233–238.

    Google Scholar 

  • Taylor, C. W., Dalton, W. S., Parrish, P. R., Gleason, M. C., Bellamy, W. T., Thompson, F. H., Roe, D. J., and Trent, J. M. (1991). Br. J. Cancer 63, 923–929.

    Google Scholar 

  • Trock, B. J., Leonessa, F., and Clarke, R. (1997). J. Natl. Cancer Inst. 89, 917–931.

    Google Scholar 

  • van den Heuvel-Eibrink, M. M., Sonneveld, P., and Pieters, R. (2000). Int. J. Clin. Pharmacol. Ther. 38, 94–110.

    Google Scholar 

  • Wallace, R. E., Lindh, D., and Durr, F. E. (1987). Cancer Invest. 5, 417–428.

    Google Scholar 

  • Yang, C. J., Horton, J. K., Cowan, K. H., and Schneider, E. (1995). Cancer Res. 55, 4004–4009.

    Google Scholar 

  • Zeng, H., Bain, L. J., Belinsky, M. G., and Kruh, G. D. (1999). Cancer Res. 59, 5964–5967.

    Google Scholar 

  • Zhang, X. P., Ritke, M. K., Yalowich, J. C., Slovak, M. L., Pelkey, H. J., Collins K. L., Annable, T., Arceci, R. J., Durr, F. E., and Greenberger, L. M. (1994). Oncol. Res. 6, 291–301.

    Google Scholar 

Download references

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bates, S.E., Robey, R., Miyake, K. et al. The Role of Half-Transporters in Multidrug Resistance. J Bioenerg Biomembr 33, 503–511 (2001). https://doi.org/10.1023/A:1012879205914

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1012879205914

Navigation