Student or educator? Sign up with your school email and get 6 months of Pro free.
Cited by 169

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Estrogen-Mediated Post transcriptional Down-regulation of Breast Cancer Resistance Protein/ABCG2

Open access
Imai, Yasuo, Ishikawa, Etsuko, Asada, Sakiyo, Sugimoto, Yoshikazu·2005·Cancer Research

Abstract

Breast cancer resistance protein (BCRP)/ABCG2 mediates concurrent resistance to chemotherapeutic agents, such as 7-ethyl-10-hydroxycamptothecin (SN-38), mitoxantrone, and topotecan, by pumping them out of cells. We previously reported that BCRP transports sulfated estrogens. In the present study, we show that at physiologic levels, estrogens markedly decrease endogenous BCRP expression in the estrogen-responsive and estrogen receptor α (ERα)–positive human breast cancer MCF-7 cells, but not in estrogen-nonresponsive human cancer cells. 17 β-Estradiol (E2) also significantly reduces exogenous BCRP expression, driven by a constitutive promoter, in BCRP-transduced estrogen-responsive and ERα-positive MCF-7 (MCF-7/BCRP) and T-47D cells, but not in BCRP-transduced estrogen-nonresponsive MDA-MB-231 and SKOV-3 cells. E2 potentiates the cytotoxicity of SN-38, but not vincristine, in MCF-7/BCRP cells significantly, and increases cellular topotecan uptake in MCF-7 and MCF-7/BCRP cells. Antiestrogen tamoxifen partially reverses E2-mediated BCRP down-regulation in MCF-7 and MCF-7/BCRP cells and treatment of MCF-7/BCRP cells with an ERα small interfering RNA abolished E2-mediated BCRP down-regulation, suggesting that interaction of E2 and ERα is necessary for BCRP down-regulation. E2 does not affect endogenous BCRP mRNA levels in MCF-7 cells or exogenous BCRP mRNA levels in MCF-7/BCRP cells. The results from pulse-chase labeling experiments with MCF-7/BCRP cells suggest that decreased protein biosynthesis and maturation, but not alterations in protein turnover, might underlie E2-mediated BCRP down-regulation. These data indicate that estrogen down-regulates BCRP expression by novel posttranscriptional mechanisms. This is the first report of small molecules that can affect BCRP protein expression in cells and may therefore assist in establishing new strategies for regulating BCRP expression.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1158/0008-5472.596.65.2

Cites

1 of 1 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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

Show all 1 references

Research works printed but not linked: 29

  1. Allikmets R, Schriml L, Hutchinson A, Romano-Spica V, Dean M. A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res 1998; 58: 5337–9.
  2. Doyle LA, Yang W, Abruzzo LV, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci U S A 1998; 95: 15665–70. · DOI · Paper page
  3. Miyake K, Mickley L, Litman T, et al. Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes. Cancer Res 1999; 59: 8–13.
  4. Maliepaard M, van Gastelen MA, de Jong LA, et al. Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res 1999; 59: 4559–63.
  5. Kawabata S, Oka M, Shiozawa K, et al. Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells. Biochem Biophys Res Commun 2001; 280: 1216–23. · DOI · Paper page
  6. Imai Y, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y. Estrone and 17β-estradiol reverse breast cancer resistance protein-mediated multidrug resistance. Jpn J Cancer Res 2002; 93: 231–5. · doi:10.1111/j.1349-7006.2002.tb02162.x
  7. Imai Y, Asada S, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y. Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol Pharmacol 2003; 64: 610–8. · DOI · Paper page
  8. Bailey-Dell KJ, Hassel B, Doyle LA, Ross DD. Promoter characterization and genomic organization of the human breast cancer resistance protein (ATP-binding cassette transporter G2) gene. Biochim Biophys Acta 2001; 1520: 234–41. · DOI · Paper page
  9. Ee PL, Kamalakaran S, Tonetti D, He X, Ross DD, Beck WT. Identification of a novel estrogen response element in the breast cancer resistance protein (ABCG2) gene. Cancer Res 2004; 64: 1247–1. · DOI · Paper page
  10. Kage K, Tsukahara S, Sugiyama T, et al. Dominant-negative inhibition of breast cancer resistance protein as drug efflux pump through the inhibition of S-S dependent homodimerization. Int J Cancer 2002; 97: 626–30. · DOI · Paper page
  11. Hua W, Christianson T, Rougeot C, Rochefort H, Clinton GM. SKOV3 ovarian carcinoma cells have functional estrogen receptor but are growth-resistant to estrogen and antiestrogens. J Steroid Biochem Mol Biol 1995; 55: 279–89. · DOI
  12. Lau KM, Mok SC, Ho SM. Expression of human estrogen receptor-α and -β, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells. Proc Natl Acad Sci U S A 1999; 96: 5722–7. · DOI · Paper page
  13. Maliepaard M, Scheffer GL, Faneyte IF, et al. Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res 2001; 61: 3458–64.
  14. Sugimoto Y, Tsukahara S, Imai Y, et al. Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists. Mol Cancer Ther 2003; 2: 105–12.
  15. Imai Y, Tsukahara S, Asada S, Sugimoto Y. Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. Cancer Res 2004; 64: 4346–52. · DOI · Paper page
  16. Murphy CS, Pink JJ, Jordan VC. Characterization of a receptor-negative, hormone-nonresponsive clone derived from a T47D human breast cancer cell line kept under estrogen-free conditions. Cancer Res 1990; 50: 7285–92.
  17. Inoue A, Yoshida N, Omoto Y, et al. Development of cDNA microarray for expression profiling of estrogen-responsive genes. J Mol Endocrinol 2002; 29: 175–92. · DOI · Paper page
  18. Coser KR, Chesnes J, Hur J, Ray S, Isselbacher KJ, Shioda T. Global analysis of ligand sensitivity of estrogen inducible and suppressible genes in MCF7/BUS breast cancer cells by DNA microarray. Proc Natl Acad Sci U S A 2003; 100: 13994–9. · DOI · Paper page
  19. Benayoun B, Esnard-Feve A, Castella S, Courty Y, Esnard F. Rat seminal vesicle FAD-dependent sulfhydryl oxidase. Biochemical characterization and molecular cloning of a member of the new sulfhydryl oxidase/quiescin Q6 gene family. J Biol Chem 2001; 276: 13830–7. · DOI
  20. Thorpe C, Hoober KL, Raje S, et al. Sulfhydryl oxidases: emerging catalysts of protein disulfide bond formation in eukaryotes. Arch Biochem Biophys 2002; 405: 1–12. · DOI · Paper page
  21. Keitel V, Kartenbeck J, Nies AT, Spring H, Brom M, Keppler D. Impaired protein maturation of the conjugate export pump multidrug resistance protein 2 as a consequence of a deletion mutation in Dubin-Johnson syndrome. Hepatology 2000; 32: 1317–28. · DOI
  22. Hashimoto K, Uchiumi T, Konno T, et al. Trafficking and functional defects by mutations of the ATP-binding domains in MRP2 in patients with Dubin-Johnson syndrome. Hepatology 2002; 36: 1236–45. · DOI
  23. Scheffer GL, Maliepaard M, Pijnenborg AC, et al. Breast cancer resistance protein is localized at the plasma membrane in mitoxantrone- and topotecan-resistant cell lines. Cancer Res 2000; 60: 2589–93.
  24. Faneyte IF, Kristel PM, Maliepaard M, et al. Expression of the breast cancer resistance protein in breast cancer. Clin Cancer Res 2002; 8: 1068–74.
  25. Diestra JE, Scheffer GL, Catala I, et al. Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material. J Pathol 2002; 198: 213–9. · DOI · Paper page
  26. McGuire WL, Chamness GC, Costlow ME, Richert NJ. Steroids and human breast cancer. J Steroid Biochem Mol Biol 1975; 6: 723–7. · doi:10.1016/0022-4731(75)90059-x
  27. Jonker JW, Buitelaar M, Wagenaar E, et al. The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc Natl Acad Sci U S A 2002; 99: 15649–54. · DOI · Paper page
  28. van Herwaarden AE, Jonker JW, Wagenaar E, et al. The breast cancer resistance protein (Bcrp1/Abcg2) restricts exposure to the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Cancer Res 2003; 63: 6447–52.
  29. Ifergan I, Shafran A, Jansen G, Hooijberg JH, Scheffer GL, Assaraf YG. Folate deprivation results in the loss of breast cancer resistance protein (BCRP/ABCG2) expression: A role for BCRP in cellular folate homeostasis. J Biol Chem 2004; 279: 25527–34. · doi:10.1074/jbc.m401725200

Cited by

See all 169

Metadata

Authors
Imai, Y., Ishikawa, E., Asada, S., & Sugimoto, Y.
Venue
Cancer Research
Published
2005-01-15
Volume
65
Issue
2
Pages
596-604
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2118386164
Cited by
169
References
1
FWCI
6.36
Type
journal article
Language
en
Open access
bronze

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: Estrogen-Mediated Post transcriptional Down-regulation of Breast Cancer Resistance Protein/ABCG2. https://app.cochat.ai/papers/10.1158/0008-5472.596.65.2
The paper
Imai, Y., Ishikawa, E., Asada, S., & Sugimoto, Y. (2005). Estrogen-Mediated Post transcriptional Down-regulation of Breast Cancer Resistance Protein/ABCG2. Cancer Research. https://doi.org/10.1158/0008-5472.596.65.2

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.