Multidrug resistance-associated protein expression in clinical gastric carcinoma

Endo, Kazuya; Maehara, Yoshihiko; Ichiyoshi, Yuji; Kusumoto, Tetsuya; Sakaguchi, Yoshihisa; Ohno, Shinji; Sugimachi, Keizō

doi:10.1002/(sici)1097-0142(19960415)77:8<1681::aid-cncr39>3.0.co;2-u

Cited by 29 publications

(7 citation statements)

References 24 publications

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“…This question may also be studied on the basis of mRNA translation from the multidrug resistance gene. Other potential influences on secretion processes such as, e.g., expression of multidrug resistance associated protein, 22 must not be neglected.…”

Section: Discussionmentioning

confidence: 99%

P-Glycoprotein (P-gp) Mediated Efflux in Caco-2 Cell Monolayers: The Influence of Culturing Conditions and Drug Exposure on P-gp Expression Levels

Anderle

Niederer

Rubas³

et al. 1998

Journal of Pharmaceutical Sciences

197

113

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The influence of cell culture conditions and previous drug exposure on P-glycoprotein (P-gp) expression levels in Caco-2 cells was determined. In this study, the expression of P-gp is demonstrated (i) visually by confocal laser scanning microscopy (CLSM), (ii) functionally by transport studies with substrates of the efflux pump, and (iii) quantitatively by flow cytometry (FCM) analysis using specific monoclonal antibodies (anti P-gp MRK 16 as an external antibody and P-GlycoCheck C219 as an internal antibody). Trypsinization of the cells after reaching confluence led to a decrease of P-gp expression levels, while trypsinization before reaching confluence led to an increase after long-term cultivation. Culturing the cells on polycarbonate filters did not elicit a significant change of P-gp expression over time in culture, whereas in plastic flasks (polystyrene) a decrease was detected. Using CLSM a strong fluorescence on the apical side of Caco-2 cell monolayers was observed, as a result of incubation with MRK 16 as primary and IgG Cy5 as secondary antibody. Previous drug exposure of the cells showed that verapamil, celiprolol, and vinblastine induced the P-gp expression, while metkephamid (MKA) decreased the P-gp expression level as compared to the control. Permeation studies consolidated the theory that P-gp is expressed in the Caco-2 cells examined. For talinolol and MKA, a higher transport from basolateral to apical side than from apical to basolateral could be measured. Incubation of the cell monolayer with MRK 16 reduced the secretion process to the apical side, but did not influence [3H]mannitol flux. Caco-2 cells seem to be a suitable cell line model for P-gp-mediated secretion studies. However, the variability of the P-gp expression requires careful control when this model is to be used in quantitative structure/secretion studies.

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Section: Discussionmentioning

confidence: 99%

P-Glycoprotein (P-gp) Mediated Efflux in Caco-2 Cell Monolayers: The Influence of Culturing Conditions and Drug Exposure on P-gp Expression Levels

Anderle

Niederer

Rubas³

et al. 1998

Journal of Pharmaceutical Sciences

197

113

View full text Add to dashboard Cite

show abstract

“…ABC transporter proteins positive tumor samples were graded from 1 to 3 according to the distribution of positivity and the degree of immunostaining of the plasma membrane or cytoplasmic Golgi region,25, 26 as follows: Score 1, positive cells are less than 10% and weak immunostaining; Score 2, more than 10% of the tumor cells are positive and weak immunostaining and Score 3, more than 10% of the tumor cells are positive and strong immunoreactivity. The highest degree of positivity found in any area of the section was recorded and grade 2 or 3 was judged as positive.…”

Section: Methodsmentioning

confidence: 99%

ATP‐binding cassette superfamily transporter gene expression in human soft tissue sarcomas

Oda

Saito

Tateishi

et al. 2004

Intl Journal of Cancer

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“…An association of p53 staining and ABCC1 was also seen in testicular tumors, however, all tumors expressed ABCC1 protein regardless of clinicopathologic variables suggesting no relationship to tumor progression 104. Coexpression of p53 and ABCC1 was not observed in breast carcinoma and gastric carcinoma 72, 79, 105. As for the role of ABCC1 in tumor progression, no correlation was observed in testicular,104 gastric105 or ovarian106 cancers, whereas an inverse relationship was detected in a breast cancer survey 72…”

Section: Correlation Of P53 and Multidrug Transporter Expression In Tmentioning

confidence: 97%

Cancer chemoresistance: The relationship between p53 and multidrug transporters

Bush

2002

Intl Journal of Cancer

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Extensive studies indicate that both p53 and multidrug transporters play important roles in chemoresistance. Since the initial reports a decade ago demonstrating a transcriptional dependence of the ABCB1 gene (MDR) promoter by p53, much data have been accumulated. However, despite being the subject of intense study, this p53-MDR relationship remains unclear in human cancers. The data are confounded by variable and contrasting results when considering the in vitro regulation and attempting to draw parallels in tissue specimens. The original model suggested that wild-type p53 downregulates the ABCB1 promoter, whereas mutant p53 increases expression of ABCB1. This review summarizes the data for and against this hypothesis. What emerges from these studies is a complex picture, where data have been obtained in support of this hypothesis, but there are also many circumstances where it is not supported. Taken together, these data suggest that the relationship between p53 and multidrug transporters is conditional. It is dependent on cellular environment, the drug used, and the nature of the p53 mutation.

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Multidrug resistance-associated protein expression in clinical gastric carcinoma

Cited by 29 publications

References 24 publications

P-Glycoprotein (P-gp) Mediated Efflux in Caco-2 Cell Monolayers: The Influence of Culturing Conditions and Drug Exposure on P-gp Expression Levels

P-Glycoprotein (P-gp) Mediated Efflux in Caco-2 Cell Monolayers: The Influence of Culturing Conditions and Drug Exposure on P-gp Expression Levels

ATP‐binding cassette superfamily transporter gene expression in human soft tissue sarcomas

Cancer chemoresistance: The relationship between p53 and multidrug transporters

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