Methods to detect P-glycoprotein and implications for other drug resistance-associated proteins

Beck, WT; Grogan, TM

doi:10.1038/sj.leu.2400675

Cited by 22 publications

(9 citation statements)

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“…The level of ABCB1 protein expression was quantified through Western immunoblotting using C219 mouse monoclonal antibody previously reported to specifically recognize ABCB1 [31,32]. We confirmed the specificity of this antibody through preincubation with the peptide epitope and prevention of binding at 170 kDa (Fig.…”

Section: Resultsmentioning

confidence: 97%

Multidrug Resistance Phosphoglycoprotein (ABCB1) in the Mouse Placenta: Fetal Protection1

Kalabis

Kostaki

Andrews

et al. 2005

Biology of Reproduction

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The multidrug resistance phosphoglycoprotein ATP-binding cassette subfamily B (ABCB1) actively extrudes a range of structurally and functionally diverse xenobiotics as well as glucocorticoids. ABCB1 is present in many cancer cell types as well as in normal tissues. Although it has been localized within the mouse placenta, virtually nothing is known about its regulation. In the mouse, two genes, Abcb1a and Abcb1b, encode ABCB1. We hypothesized that there are changes in placental Abcb1a and Abcb1b gene expression and ABCB1 protein levels during pregnancy. Using in situ hybridization, we demonstrated that Abcb1b mRNA is the predominant placental isoform and that there are profound gestational changes in the expression of both Abcb1a and Abcb1b mRNA. Placentas from pregnant mice were analyzed between Embryonic Days (E) 9.5 and 19 (term approximately 19.5d). Abcb1b mRNA was detected in invading trophoblast cells by E9.5, peaked within the placental labyrinth at E12.5, and then progressively decreased toward term (P < 0.0001). Abcb1a mRNA, although lower than that of Abcb1b at midgestation, paralleled changes in Abcb1b mRNA. Changes in Abcb1 mRNA were reflected by a significant decrease in ABCB1 protein (P < 0.05). A strong correlation existed between placental Abcb1b mRNA and maternal progesterone concentrations, indicating a potential role of progesterone in regulation of placental Abcb1b mRNA. In conclusion, there are dramatic decreases in Abcb1a and Abcb1b mRNA and in ABCB1 at the maternal-fetal interface over the second half of gestation, suggesting that the fetus may become increasingly susceptible to the influences of xenobiotics and natural steroids in the maternal circulation.

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Section: Resultsmentioning

confidence: 97%

Multidrug Resistance Phosphoglycoprotein (ABCB1) in the Mouse Placenta: Fetal Protection1

Kalabis

Kostaki

Andrews

et al. 2005

Biology of Reproduction

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“…Among the multiple mechanisms of multidrug resistance, overexpression of P-gp has emerged as the main factor involved in that process. P-gp is a 170 kDa product of the multidrug resistance-1 (MDR-1) gene [15]. The transcription of MDR-1 is directly regulated by human Y-box-binding protein-1 (YB-1), an MDR-1 transcription factor.…”

Section: Discussionmentioning

confidence: 99%

Expression of P-glycoprotein in lymphocytes from children with nephrotic syndrome, depending on their steroid response

et al. 2006

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The aim of this study was to examine the expression of P-glycoprotein (P-gp) in CD3 lymphocytes of children with nephrotic syndrome (NS) in relation to their clinical response to glucocorticoid (GC) treatment. The examinations were performed on two groups. The study group (I) consisted of 88 children aged 2.0-20.0 years with NS, divided according to their clinical response to GC: NFR-non-frequent relapse NS; FR-frequent relapse NS; SD-steroid-dependent NS. The control group (II) consisted of 18 healthy children never treated with GC. We measured P-gp expression on CD3 lymphocytes of patients with NS using a flow cytometry assay. The CD3/P-gp was significantly higher than in controls. The difference was higher in SD (P=0.0001) and FR - (P=0.0002) group. The difference in NFR was smaller. Mean CD3/P-gp (in percent) was twice as high in SD children than in NFR, and the difference, as between FR and NFR, was statistically significant (P<0.01). Worse response to GC or dependency may be due to overexpression of P-gp. Further examinations are necessary to establish whether increased P-gp activity is a result of MDR-1 polymorphism and to determine GC response, or to ascertain if such activity is only a result of GC therapy.

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“…In fact, a careful analysis of the reports on MDR1 expression in MM shows the existence of disturbing levels of variability as regards both its overexpression and its clinical impact. Accordingly, at present, one of the major concerns regarding the analysis of MDR1 expression in human neoplasias is to select the most appropriate method for the assessment of its functionality (34). In this sense, a conference held in Memphis, Tennessee in 1994 (35) Results expressed as number of cases and (b) median (range).…”

Section: Discussionmentioning

confidence: 99%

Correlation of rhodamine 123 efflux by neoplastic plasma cells with clinical and biological characteristics of multiple myeloma

Pérez‐Simón¹,

Valverde²,

Martínez³

et al. 1999

Cytometry

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Although a variable proportion of multiple myeloma patients can achieve response with conventional chemotherapy, residual tumor cells, which are refractory, finally reemerge leading to disease progression. The expression of the multidrug resistance protein (MDR1) has been one of the most extensively explored mechanisms of drug resistance and has been related to a poor response to chemotherapy in several human tumors. Nevertheless, a careful analysis of the literature on MDR1 expression in multiple myeloma (MM) shows the existence of disturbing discrepancies as regards both the incidence of MDR1 over-expression and its clinical value. A prerequisite for the assessment of MDR1 in tumor cells should be the identification of the neoplastic cells present in the sample. This is particularly important in MM, where the percentage of tumor cells in bone marrow (BM) is relatively low. In the present study we have analyzed the functional expression of MDR1 in BM plasma cells (PC), from a group of 40 untreated MM patients. For that purpose, the rhodamine 123 efflux assay was used in combination with specific staining for plasma cells (CD38 strong+). The mean fluorescence channel (MFC) of rhodamine 123 in myelomatous PC from MM patients was 311 and 110 after incubating cells with this fluorochrome for 15 and 60 min, respectively. The median percentage of rhodamine 123 elimination by BM PC was of 61% (range: 0.29 to 88%). Upon analyzing the relationship between the ability of myelomatous PC to eliminate rhodamine 123 and other clinical and biological disease characteristics we found that, within the group of patients displaying high MDR1 expression (>61% rhodamine efflux), there was a higher incidence of cases with bone disease (P = 0.014) and advanced clinical stages (P = 0.031), greater calcium (P = 0.007) and creatinine serum levels (P = 0.061), and lower levels of albumin in serum (P = 0.015). All these parameters are usually associated with a poor prognosis. When we analyzed the possible relationship between the ability of BM PC to eliminate rhodamine 123 and the presence of numerical chromosome abnormalities we observed that a low MDR1 expression was related to a higher incidence of trisomies of chromosomes 6 and 17, although these differences did not reach statistical significance (P = 0.06). In spite of these associations, from the prognostic point of view, MDR1 expression did not correlate with other relevant prognostic factors, response to treatment (P = 0.38) or overall survival (P = 0.12).

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Methods to detect P-glycoprotein and implications for other drug resistance-associated proteins

Cited by 22 publications

References 1 publication

Multidrug Resistance Phosphoglycoprotein (ABCB1) in the Mouse Placenta: Fetal Protection1

Multidrug Resistance Phosphoglycoprotein (ABCB1) in the Mouse Placenta: Fetal Protection1

Expression of P-glycoprotein in lymphocytes from children with nephrotic syndrome, depending on their steroid response

Correlation of rhodamine 123 efflux by neoplastic plasma cells with clinical and biological characteristics of multiple myeloma

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