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Titolo:
Overexpression of the ATP-binding cassette half-transporter, ABCG2 (MXR/BCRP/ABCP1), in flavopiridol-resistant human breast cancer cells
Autore:
Robey, RW; Medina-Perez, WY; Nishiyama, K; Lahusen, T; Miyake, K; Litman, T; Senderowicz, AM; Ross, DD; Bates, SE;
Indirizzi:
NCI, Med Branch, Dev Therapeut Dept, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 Dev Therapeut Dept, NIH, Bethesda, MD 20892 USA Natl Inst Dent & Craniofacial Res, Mol Therapeut Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA Natl Inst Dent & Craniofacial Res Bethesda MD USA 20892 sda, MD 20892 USA Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA Univ MarylandBaltimore MD USA 21201 um Canc Ctr, Baltimore, MD 21201 USA Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 d, Dept Med, Baltimore, MD 21201 USA Baltimore Vet Med Ctr, Dept Vet Affairs, Baltimore, MD 21201 USA BaltimoreVet Med Ctr Baltimore MD USA 21201 irs, Baltimore, MD 21201 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 1, volume: 7, anno: 2001,
pagine: 145 - 152
SICI:
1078-0432(200101)7:1<145:OOTACH>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT KINASE INHIBITOR; MULTIDRUG-RESISTANCE; DRUG-SENSITIVITY; CARCINOMA CELLS; PROTEIN GENE; CYCLE ARREST; APOPTOSIS; EXPRESSION; LINES; CYTOTOXICITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Bates, SE NCI, Med Branch, Dev Therapeut Dept, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA NCI Bldg 10,Room 12N226,9000 Rockville Pike Bethesda MD USA 20892
Citazione:
R.W. Robey et al., "Overexpression of the ATP-binding cassette half-transporter, ABCG2 (MXR/BCRP/ABCP1), in flavopiridol-resistant human breast cancer cells", CLIN CANC R, 7(1), 2001, pp. 145-152

Abstract

We sought to characterize the interactions of flavopiridol with members ofthe ATP-binding cassette (ABC) transporter family, Cells overexpressing multidrug resistance-1 (MDR-1) and multidrug resistance-associated protein (MRP) did not exhibit appreciable flavopiridol resistance, whereas cell linesoverexpressing the ABC half-transporter, ABCG2, (MXR/BCRP/ABCP1), were found to be resistant to flavopiridol, Flavopiridol at a concentration of 10 muM was able to prevent MRP-mediated calcein efflux, whereas Pgp-mediated transport of rhodamine 123 was unaffected at flavopiridol concentrations of up to 100 muM. To determine putative mechanisms of resistance to flavopiridol, we exposed the human breast cancer cell line MCF-7 to incrementally increasing concentrations of flavopiridol, The resulting resistant subline, MCF-7 FLV1000, is maintained in 1000 nM flavopiridol and was found to be 24-fold resistant to flavopiridol, as well as highly cross-resistant to mitoxantrone (675-fold), topotecan (423-fold), and SN-38 (950-fold), the active metabolite of irinotecan, Because this cross-resistance pattern is consistent with that reported for ABCG2-overexpressing cells, cytotoxicity studies were repeated in the presence of 5 muM Of the ABCG2 inhibitor fumitremorgin C (FTC), and sensitivity of MCF-7 FLV1000 cells to flavopiridol, mitoxantrone, SN-38, and topotecan was restored. Mitoxantrone efflux studies were performed, and high levels of FTC-reversible mitoxantrone efflux were found. Northern blot and PCR analysis revealed overexpression of the ABCG2 gene. Western blot confirmed overexpression of ABCG2; neither P-glycoprotein nor MRP overexpression was detected. These results suggest that ABCG2 plays a role in resistance to flavopiridol.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 07:02:54