The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Mrp4 Confers Resistance to Topotecan and Protects the Brain from Chemotherapy
Open accessAbstract
The role of the multidrug resistance protein MRP4/ABCC4 in vivo remains undefined. To explore this role, we generated Mrp4-deficient mice. Unexpectedly, these mice showed enhanced accumulation of the anticancer agent topotecan in brain tissue and cerebrospinal fluid (CSF). Further studies demonstrated that topotecan was an Mrp4 substrate and that cells overexpressing Mrp4 were resistant to its cytotoxic effects. We then used new antibodies to discover that Mrp4 is unique among the anionic ATP-dependent transporters in its dual localization at the basolateral membrane of the choroid plexus epithelium and in the apical membrane of the endothelial cells of the brain capillaries. Microdialysis sampling of ventricular CSF demonstrated that localization of Mrp4 at the choroid epithelium is integral to its function in limiting drug penetration into the CSF. The topotecan resistance of cells overexpressing Mrp4 and the polarized expression of Mrp4 in the choroid plexus and brain capillary endothelial cells indicate that Mrp4 has a dual role in protecting the brain from cytotoxins and suggest that the therapeutic efficacy of central nervous system-directed drugs that are Mrp4 substrates may be improved by developing Mrp4 inhibitors.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302
Carmichael, J., DeGraff, W., Gazdar, A. F., Minna, J. D., & Mitchell, J. B. (1987) · PubMed · Cited by 3,813
Schinkel, A. H., Smit, J. J. M., van Tellingen, O., Beijnen, J. H., Wagenaar, E., van Deemter, L., Mol, C. A. A. M., van der Valk, M. A., Robanus-Maandag, E. C., te Riele, H. P. J., et al. (1994) · Cell · doi:10.1016/0092-8674(94)90212-7 · Cited by 2,281
The Human ATP-Binding Cassette (ABC) Transporter Superfamily
Dean, M., Rzhetsky, A., & Allikmets, R. (2001) · Genome Research · doi:10.1101/gr.184901 · Cited by 1,748
Mammalian ABC Transporters in Health and Disease
Borst, P., & Elferink, R. O. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.102301.093055 · Cited by 1,571
Ansar Ahmed, S., Gogal, R. M., & Walsh, J. E. (1994) · Journal of Immunological Methods · doi:10.1016/0022-1759(94)90396-4 · Cited by 1,359
Samad, T. A., Moore, K. A., Sapirstein, A., Billet, S., Allchorne, A., Poole, S., Bonventre, J. V., & Woolf, C. J. (2001) · Nature · doi:10.1038/35068566 · Cited by 1,281
THE CELL BIOLOGY OF THE BLOOD-BRAIN BARRIER
Rubin, L. L., & Staddon, J. M. (1999) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.22.1.11 · Cited by 1,000
MRP4: A previously unidentified factor in resistance to nucleoside-based antiviral drugs
Schuetz, J. D., Connelly, M. C., Sun, D., Paibir, S. G., Flynn, P. M., Srinivas, R. V., Kumar, A., & Fridland, A. (1999) · Nature Medicine · doi:10.1038/12487 · Cited by 575
Self-citationRao, V. V., Dahlheimer, J. L., Bardgett, M. E., Snyder, A. Z., Finch, R. A., Sartorelli, A. C., & Piwnica-Worms, D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3900 · Cited by 531
Cited by
Targeting multidrug resistance in cancer
Szakács, G., Paterson, J. K., Ludwig, J. A., Booth-Genthe, C., & Gottesman, M. M. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd1984 · Cited by 3,609
Helms, H. C., Abbott, N. J., Burek, M., Cecchelli, R., Couraud, P.-O., Deli, M. A., Förster, C., Galla, H. J., Romero, I. A., Shusta, E. V., et al. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16630991 · Cited by 843
Deeley, R. G., Westlake, C., & Cole, S. P. C. (2006) · Physiological Reviews · doi:10.1152/physrev.00035.2005 · Cited by 761
Ohtsuki, S., & Terasaki, T. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9374-5 · Cited by 454
ABC transporters as mediators of drug resistance and contributors to cancer cell biology
Fletcher, J. I., Williams, R. T., Henderson, M. J., Norris, M. D., & Haber, M. (2016) · Drug Resistance Updates · doi:10.1016/j.drup.2016.03.001 · Cited by 423
Metadata
- Authors
- Leggas, M., Adachi, M., Scheffer, G. L., Sun, D., Wielinga, P., Du, G., Mercer, K. E., Zhuang, Y., Panetta, J. C., Johnston, B., Scheper, R. J., Stewart, C. F., & Schuetz, J. D.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-09-01
- Volume
- 24
- Issue
- 17
- Pages
- 7612-7621
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2106762675
- Cited by
- 414
- References
- 44
- FWCI
- 11.60
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Mrp4 Confers Resistance to Topotecan and Protects the Brain from Chemotherapy. https://app.cochat.ai/papers/10.1128/mcb.24.17.7612-7621.2004
- The paper
- Leggas, M., Adachi, M., Scheffer, G. L., Sun, D., Wielinga, P., Du, G., Mercer, K. E., Zhuang, Y., Panetta, J. C., Johnston, B., Scheper, R. J., Stewart, C. F., & Schuetz, J. D. (2004). Mrp4 Confers Resistance to Topotecan and Protects the Brain from Chemotherapy. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.24.17.7612-7621.2004
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
