Int J Cancer. 1996 Mar 1;65(5):613-9.

Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate.

Norris MD, De Graaf D, Haber M, Kavallaris M, Madafiglio J, Gilbert J, Kwan E, Stewart BW, Mechetner EB, Gudkov AV, Roninson IB.

Source

Children's Leukaemia and Cancer Research Centre, Prince of Wales Children's Hospital, Sydney, Australia.

Abstract

Cellular resistance to methotrexate (MTX) is believed to be unaffected by expression of MDR1 P-glycoprotein (Pgp), a pleiotropic efflux pump acting on different hydrophobic compounds that enter cells by passive diffusion. A series of human leukemic CCRF-CEM sublines, isolated by multi-step selection for very high resistance to MTX, exhibit multiple mechanisms of MTX resistance, including decreased carrier-mediated uptake of MTX and DHFR gene amplification. These sublines show cross-resistance to drugs of the multi-drug resistance (MDR) family, which is correlated with relative resistance to MTX. The MTX-selected sublines show increased expression and function of the MDR1 gene, based on the measurement of MDR1 mRNA, Pgp and rhodamine 123 accumulation. Sequence analysis of the MDR1 cDNA from MTX-selected CCRF-CEM cells revealed no mutations in the protein coding region. MTX resistance in these cell lines is partially reversible by a Pgp-specific monoclonal antibody (MAb) UIC2 and a monovalent FaB fragment of UIC2. Our results indicate that Pgp can contribute to multifactorial resistance to MTX.

PMID:: 8598312; [PubMed - indexed for MEDLINE]

LinkOut - more resources

Full Text Sources

Other Literature Sources

COS Scholar Universe

Molecular Biology Databases

Supplemental Content

Save items

Related citations in PubMed

P-glycoprotein-mediated methotrexate resistance in CCRF-CEM sublines deficient in methotrexate accumulation due to a point mutation in the reduced folate carrier gene. [Int J Cancer. 1998]
P-glycoprotein-mediated methotrexate resistance in CCRF-CEM sublines deficient in methotrexate accumulation due to a point mutation in the reduced folate carrier gene.
Gifford AJ, Kavallaris M, Madafiglio J, Matherly LH, Stewart BW, Haber M, Norris MD. Int J Cancer. 1998 Oct 5; 78(2):176-81.
P-glycoprotein confers methotrexate resistance in 3T6 cells with deficient carrier-mediated methotrexate uptake. [Proc Natl Acad Sci U S A. 1996]
P-glycoprotein confers methotrexate resistance in 3T6 cells with deficient carrier-mediated methotrexate uptake.
de Graaf D, Sharma RC, Mechetner EB, Schimke RT, Roninson IB. Proc Natl Acad Sci U S A. 1996 Feb 6; 93(3):1238-42.
Large diversity in transport-mediated methotrexate resistance in human leukemia cell line CCRF-CEM established in a high concentration of leucovorin. [Cancer Sci. 2003]
Large diversity in transport-mediated methotrexate resistance in human leukemia cell line CCRF-CEM established in a high concentration of leucovorin.
Asai S, Miyachi H, Kobayashi H, Takemura Y, Ando Y. Cancer Sci. 2003 Feb; 94(2):210-4.
Review Modulation and prevention of multidrug resistance by inhibitors of P-glycoprotein. [Cancer Chemother Pharmacol. 1997]
Review Modulation and prevention of multidrug resistance by inhibitors of P-glycoprotein.
Sikic BI, Fisher GA, Lum BL, Halsey J, Beketic-Oreskovic L, Chen G. Cancer Chemother Pharmacol. 1997; 40 Suppl:S13-9.
Review Multidrug resistance: molecular mechanisms and clinical relevance. [Cancer Chemother Pharmacol. 1997]
Review Multidrug resistance: molecular mechanisms and clinical relevance.
Ling V. Cancer Chemother Pharmacol. 1997; 40 Suppl:S3-8.

See reviews... See all...

Cited by 1 PubMed Central article

Overexpression of S100A4 in human cancer cell lines resistant to methotrexate. [BMC Cancer. 2010]
Overexpression of S100A4 in human cancer cell lines resistant to methotrexate.
Mencía N, Selga E, Rico I, de Almagro MC, Villalobos X, Ramirez S, Adan J, Hernández JL, Noé V, Ciudad CJ. BMC Cancer. 2010 Jun 1; 10:250. Epub 2010 Jun 1.

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate.
Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate.
Int J Cancer. 1996 Mar 1 ;65(5):613-9.

PubMed
Drosophila TFIID binds to a conserved downstream basal promoter element that is ...
Drosophila TFIID binds to a conserved downstream basal promoter element that is present in many TATA-box-deficient promoters.
Genes Dev. 1996 Mar 15 ;10(6):711-24.

PubMed
Incidence and clinical characterization of unprovoked seizures in adults: a pros...
Incidence and clinical characterization of unprovoked seizures in adults: a prospective population-based study.
Epilepsia. 1996 Mar ;37(3):224-9.

PubMed
Activated partial thromboplastin time and outcome after thrombolytic therapy for...
Activated partial thromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I trial.
Circulation. 1996 Mar 1 ;93(5):870-8.

PubMed
Heart rate variability: standards of measurement, physiological interpretation a...
Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology.
Circulation. 1996 Mar 1 ;93(5):1043-65.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to:

Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate.

Source

Abstract

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

LinkOut - more resources

Full Text Sources

Other Literature Sources

Molecular Biology Databases

Supplemental Content

Save items

Related citations in PubMed

Cited by 1 PubMed Central article

Related information

Recent activity

Simple NCBI Directory

Getting Started

Resources

Popular

Featured

NCBI Information