The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
The Stem Cell Marker Bcrp/ABCG2 Enhances Hypoxic Cell Survival through Interactions with Heme
Open accessAbstract
Our studies demonstrate that the ABC transporter and marker of stem and progenitor cells known as the breast cancer resistance protein (BCRP or ABCG2) confers a strong survival advantage under hypoxic conditions. We show that, under hypoxia, progenitor cells from Bcrp(-)/(-)mice have a reduced ability to form colonies as compared with progenitor cells from Bcrp(+/+) mice. Blocking BCRP function in Bcrp(+/+) progenitor cells markedly reduces survival under hypoxic conditions. However, blocking heme biosynthesis reverses the hypoxic susceptibility of Bcrp(-/-) progenitor cells, a finding that indicates that heme molecules (i.e. porphyrins) are detrimental to Bcrp(-/-) cells under hypoxia. BCRP specifically binds heme, and cells lacking BCRP accumulate porphyrins. Finally, Bcrp expression is up-regulated by hypoxia, and we demonstrate that this up-regulation involves the hypoxia-inducible transcription factor complex HIF-1. Collectively, our findings suggest that cells can, upon hypoxic demand, use BCRP to reduce heme or porphyrin accumulation, which can be detrimental to cells. Our findings have implications for the survival of stem cells and tumor cells in hypoxic environments.
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Cites
A cell initiating human acute myeloid leukaemia after transplantation into SCID mice
Lapidot, T., Sirard, C., Vormoor, J., Murdoch, B., Hoang, T., Caceres-Cortes, J., Minden, M., Paterson, B., Caligiuri, M. A., & Dick, J. E. (1994) · Nature · doi:10.1038/367645a0 · Cited by 4,783
Zhou, S., Schuetz, J. D., Bunting, K. D., Colapietro, A.-M., Sampath, J., Morris, J. J., Lagutina, I., Grosveld, G. C., Osawa, M., Nakauchi, H., et al. (2001) · Nature Medicine · doi:10.1038/nm0901-1028 · Cited by 2,280
Self-citationOn the enzymic defects in hereditary tyrosinemia.
Lindblad, B., Lindstedt, S., & Steen, G. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.10.4641 · Cited by 447
Cited by
Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy
Semenza, G. L. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.01.005 · Cited by 1,514
Mechanisms of Cell Protection by Heme Oxygenase-1
Gozzelino, R., Jeney, V., & Soares, M. P. (2010) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105600 · Cited by 1,241
Hypoxia-Inducible Factors, Stem Cells, and Cancer
Keith, B., & Simon, M. C. (2007) · Cell · doi:10.1016/j.cell.2007.04.019 · Cited by 1,179
Integration of Oxygen Signaling at the Consensus HRE
Wenger, R. H., Stiehl, D. P., & Camenisch, G. (2005) · Science's STKE · doi:10.1126/stke.3062005re12 · Cited by 1,032
Targeting cellular metabolism to improve cancer therapeutics
Zhao, Y., Butler, E. B., & Tan, M. (2013) · Cell Death & Disease · doi:10.1038/cddis.2013.60 · Cited by 989
Metadata
- Authors
- Krishnamurthy, P., Ross, D. D., Nakanishi, T., Bailey-Dell, K., Zhou, S., Mercer, K. E., Sarkadi, B., Sorrentino, B. P., & Schuetz, J. D.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-06
- Volume
- 279
- Issue
- 23
- Pages
- 24218-24225
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2104711019
- Cited by
- 661
- References
- 3
- FWCI
- 18.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Krishnamurthy, P., Ross, D. D., Nakanishi, T., Bailey-Dell, K., Zhou, S., Mercer, K. E., Sarkadi, B., Sorrentino, B. P., & Schuetz, J. D. (2004). The Stem Cell Marker Bcrp/ABCG2 Enhances Hypoxic Cell Survival through Interactions with Heme. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m313599200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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