✦ LIBER ✦

Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate

✍ Scribed by Murray D. Norris; David De Graaf; Michelle Haber; Maria Kavallaris; Janice Madafiglio; Jayne Gilbert; Edward Kwan; Bernard W. Stewart; Eugene B. Mechetner; Andrei V. Gudkov; Igor B. Roninson

Publisher: John Wiley and Sons
Year: 1996
Tongue: French
Weight: 881 KB
Volume: 65
Category: Article
ISSN: 0020-7136
DOI: 10.1002/(sici)1097-0215(19960301)65:5<613::aid-ijc10>3.0.co;2-8

No coin nor oath required. For personal study only.

✦ Synopsis

Cellular resistance to methotrexate (MTX) is believed to be unaffected by expression of MDRl 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 MDR I gene, based on the measurement of MDR I mRNA, Pgp and rhodamine I23 accumulation. Sequence analysis of the MDR I 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) UlC2 and a monovalent Fab fragment of UIC2. Our results indicate that Pgp can contribute to multifactorial resistance to MTX.

📜 SIMILAR VOLUMES

Increased MDR1 P-glycoprotein expression

Increased MDR1 P-glycoprotein expression in methotrexate resistance: Comment on the article by Yudoh et al

✍ Proton Rahman; Donna Hefferton; Desmond Robb 📂 Article 📅 2000 🏛 John Wiley and Sons 🌐 English ⚖ 66 KB 👁 1 views

Expression of multidrug-resistance P-gly

Expression of multidrug-resistance P-glycoprotein (MDR1) in human brain tumors

✍ Michel Demeule; Daniel Shedid; Édith Beaulieu; Rolando F. Del Maestro; Albert Mo 📂 Article 📅 2001 🏛 John Wiley and Sons 🌐 French ⚖ 129 KB 👁 1 views

Multidrug resistance (MDR) is associated with the expression of P-glycoprotein (P-gp), an ATP-dependent transporter which expels anti-cancer drugs from cells. In the present study, MDR1 P-gp was immunodetected by Western blot analysis in 60 human brain tumors, including meningiomas, schwannomas, low

Expression of the MDR1 gene product P-gl

Expression of the MDR1 gene product P-glycoprotein in childhood neuroblastoma

✍ Catharina R. M. Dhooge; Barbara M. J. De Moerloose; Yves C. M. Benoit; Nadine Va 📂 Article 📅 1997 🏛 John Wiley and Sons 🌐 English ⚖ 148 KB 👁 2 views

expression of the multidrug resistance gene (MDR1) product P-gp in neuroblastoma (NB) is still a matter of debate. In this study, the role of the expression

Determination of P-glycoprotein, MDR-rel

Determination of P-glycoprotein, MDR-related protein 1, breast cancer resistance protein, and lung-resistance protein expression in leukemic stem cells of acute myeloid leukemia

✍ Lorena L. de Figueiredo-Pontes; Maria-Carolina T. Pintão; Luciana C. O. Oliveira 📂 Article 📅 2008 🏛 John Wiley and Sons 🌐 English ⚖ 260 KB

P-glycoprotein-mediated methotrexate res

P-glycoprotein-mediated methotrexate resistance in CCRF-CEM sublines deficient in methotrexate accumulation due to a point mutation in the reduced folate carrier gene

✍ Andrew J. Gifford; Maria Kavallaris; Janice Madafiglio; Larry H. Matherly; Berna 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 French ⚖ 128 KB

We have previously described a series of methotrexate (MTX)-selected CCRF-CEM sublines (CEM/MTX R1-3) displaying increased resistance to drugs associated with the multidrug resistance phenotype and have provided evidence that MDR1 P-glycoprotein contributes to multifactorial MTX resistance in these

P-glycoprotein epitope mapping. II. The

P-glycoprotein epitope mapping. II. The murine monoclonal antibody MM6.15 to human multidrug-resistant cells binds with three distinct loops in the MDR1-P-glycoprotein extracellular domain

✍ Maurizio Cianfriglia; Giulia Romagnoli; Marina Tombesi; Francesca Poloni; Giulia 📂 Article 📅 1995 🏛 John Wiley and Sons 🌐 French ⚖ 980 KB

A new murine monoclonal antibody (MAb), MM6.15, to human MDRl P-glycoprotein was found to be reactive in ELISA with synthetic peptides selected from the predicted sequences of the first, fourth and sixth extracellular loop of MDRI-Pglycoprotein. In order to precisely define the MM6. 15-binding site,