The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype

Zhou, Sheng; Schuetz, John D.; Bunting, Kevin D.; Colapietro, Anne-Marie; Sampath, Janardhan; Morris, John J.; Lagutina, Irina; Grosveld, Gerard; Osawa, Mitsujiro; Nakauchi, Hiromitsu; Sorrentino, Brian P.

doi:10.1038/nm0901-1028

Cited by 2,063 publications

(1,887 citation statements)

References 31 publications

Supporting

Mentioning

1,798

Contrasting

Unclassified

Order By: Relevance

“…However, since mice deficient in P-gp had a normal number of bone marrow SP cells, it was concluded that P-gp is not required for the SP phenotype. A more detailed examination of other ABC transporters in bone marrow cells of P-gp knockout mice revealed high levels of Bcrp1 mRNA and distinct levels of Mrp1, Mrp3 and Mrp4 mRNA (Zhou et al, 2001). The notion that only BCRP can efflux Hoechst demonstrated that this transporter was dominantly associated with the SP phenotype, which was further confirmed by BCRP transfection in bone marrow cells causing significant expansion of cells bearing the SP phenotype (Zhou et al, 2001).…”

Section: Bcrp In Stem Cellsmentioning

confidence: 90%

“…A more detailed examination of other ABC transporters in bone marrow cells of P-gp knockout mice revealed high levels of Bcrp1 mRNA and distinct levels of Mrp1, Mrp3 and Mrp4 mRNA (Zhou et al, 2001). The notion that only BCRP can efflux Hoechst demonstrated that this transporter was dominantly associated with the SP phenotype, which was further confirmed by BCRP transfection in bone marrow cells causing significant expansion of cells bearing the SP phenotype (Zhou et al, 2001). Also in Bcrp1/Mdr1a/1b triple knockout mice, it was shown that Bcrp1, but not Mdr1a/1b, is responsible for the SP phenotype in the bone marrow, while both transporters are required for the SP phenotype in the mammary gland (Jonker et al, 2005).…”

Section: Bcrp In Stem Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Drug transporters: recent advances concerning BCRP and tyrosine kinase inhibitors

2008

View full text Add to dashboard Cite

show abstract

Section: Bcrp In Stem Cellsmentioning

confidence: 90%

Section: Bcrp In Stem Cellsmentioning

confidence: 99%

Drug transporters: recent advances concerning BCRP and tyrosine kinase inhibitors

2008

View full text Add to dashboard Cite

show abstract

“…35 In a murine system, it could be demonstrated that BCRP expression was highly conserved in primitive stem cells from a variety of sources including hematopoietic and embryonic stem cells. The level of BCRP protein expression directly correlated with the stem cellcharacterizing side population phenotype.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the atypical multidrug-resistant phenotype by a hammerhead ribozyme directed against the ABC transporter BCRP/MXR/ABCG2

et al. 2002

View full text Add to dashboard Cite

The phenomenon of multidrug resistance ( MDR ) in human cancers is one of the major causes of failure of chemotherapy. A recently identified new member of the superfamily of ATP -binding cassette transporters, breast cancer resistance protein ( BCRP ), was demonstrated to confer an atypical multidrug -resistant phenotype to tumor cells. To overcome the BCRP -mediated drug resistance, a specific anti -BCRP hammerhead ribozyme was introduced into the human gastric carcinoma cell line, EPG85 -257RNOV, exhibiting an atypical MDR phenotype. By this approach, the expression levels of the targeted BCRP -encoding mRNA and the BCRP transport protein were decreased to the low constitutive expression level that was observed in highly drug -sensitive parental gastric carcinoma cells. In addition, in the anti -BCRP ribozyme -treated cells, the cellular drug accumulation was dramatically increased to the level measured in drug -sensitive cells. These effects were accompanied by an extensive reversal of the drug -resistant phenotype of more than 80%. Because additional mechanisms contribute to the multimodal -mediated MDR phenotype exhibited by this gastric carcinoma cell line, the data suggest that the BCRP -mediated contingent to the drug resistance was overcome nearly completely. Moreover, the data indicate that ribozyme -based gene therapy may be clinically applicable in preventing and reversing BCRPmediated atypical MDR.

show abstract

“…SP cells were initially identified in mouse bone marrow as long-term repopulating cells (Goodell et al, 1997). This original discovery was followed by other reports on a wide variety of tissues (Zhou et al, 2001). High expression of ABCG2 in hematopoietic stem cells was also reported (Scharenberg et al, 2002).…”

Section: Reduction Of Sp Cells In Gastric Cancer By Tgf-b S Ehata Et Almentioning

confidence: 98%

Transforming growth factor-β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells

et al. 2010

View full text Add to dashboard Cite

Stem cells in normal tissues and cancer-initiating cells (CICs) are known to be enriched in side population (SP) cells. However, the factors responsible for the regulation of expression of ABCG2, involved in efflux of dyes, in SP cells have not been fully investigated. Here, we characterized the SP cells within diffuse-type gastric carcinoma, and examined the effects of transforming growth factor-b (TGF-b) on SP cells. Diffuse-type gastric carcinoma cells established from four independent patients universally contained SP cells between 1 and 4% of total cells, which displayed greater tumorigenicity than non-SP cells did. TGF-b repressed the transcription of ABCG2 through direct binding of Smad2/3 to its promoter/enhancer, and the number of SP cells and the tumor-forming ability of cancer cells were decreased by TGF-b, although ABCG2 is not directly involved in the tumor-forming ability of SP cells. Cancer cells from metastatic site expressed much higher levels of ABCG2 and included a greater percentage of SP cells than parental cancer cells did. SP cells are thus responsible for the progression of diffuse-type gastric carcinoma, and TGF-b negatively contributes to maintain the CICs within the cancer.

show abstract

The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype

Cited by 2,063 publications

References 31 publications

Drug transporters: recent advances concerning BCRP and tyrosine kinase inhibitors

Drug transporters: recent advances concerning BCRP and tyrosine kinase inhibitors

Modulation of the atypical multidrug-resistant phenotype by a hammerhead ribozyme directed against the ABC transporter BCRP/MXR/ABCG2

Transforming growth factor-β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells

Contact Info

Product

Resources

About