Investigation of MRP‐1 protein and MDR‐1 P‐glycoprotein expression in invasive breast cancer: A prognostic study

Larkin, Annemarie; O’Driscoll, Lorraine; Kennedy, Susan; Purcell, Rachel; Morán, Elizabeth; Crown, John; Parkinson, Michael; Clynes, Martin

doi:10.1002/ijc.20369

Cited by 81 publications

(50 citation statements)

References 25 publications

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“…Although the role of MDR1 and MRP1 in inducing drug resistance in many cancers has been widely investigated the data is still controversial (2,9,10,11). Therefore, the aim of the present study was to analyze the expression of MDR1 and MRP1 in breast cancer patients to see whether or not the expression of either of these genes or in combination or could be used as a marker to predict of drug sensitivity.…”

Section: Introductionmentioning

confidence: 98%

MRP1 but Not MDR1 Is Associated with Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

Taheri

Mahjoubi

2013

Disease Markers

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Abstract. A major problem in the treatment of breast cancer is the development of resistance to chemotherapeutic agents. Although the role of multidrug resistance 1 (MDR1) and multidrug resistance associated protein 1 (MRP1) in inducing drug resistance in many cancers has been widely investigated the clinical significance of expression of these genes in breast cancer remains unclear and the data is still controversial. We investigated the expression of MDR1 and MRP1 in breast cancer patients as well as the possible correlation between MDR1 and MRP1 and clinical response to chemotherapy. In the present study, MDR1 and MRP1 gene expression were investigated by real time reverse transcription polymerase chain reaction (RT-PCR) assay in 54 breast cancer tumors and in corresponding adjacent normal tissues before neoadjuvant chemotherapy. The expression level of MDR1 and MRP1 were significantly higher in breast tumors than normal breast tissues. Although a significant relationship was found between the MRP1 expression and response to treatment no association was observed between MDR1 expression and response to treatment. MDR1 and MRP1 expression levels have been shown to be independent of tumor size, histological grade and the status of progesterone or estrogen receptor.

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Section: Introductionmentioning

confidence: 98%

MRP1 but Not MDR1 Is Associated with Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

Taheri

Mahjoubi

2013

Disease Markers

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“…In addition to cancer cells, P-glycoprotein is expressed in epithelial cells of normal tissues involved in drug disposition including the liver, intestine, and kidney while providing a barrier to sites such as the brain and testes (Marzolini et al, 2004). P-Glycoprotein expression has been noted to be highly variable in primary breast tumors (detection ranging from 9 to 50% of tumors examined) and is significantly increased after treatment with chemotherapeutic agents; however, its significance to chemotherapy clinical response remains controversial (Koh et al, 1992;Tsukamoto et al, 1997;Rudas et al, 2003;Larkin et al, 2004;Atalay et al, 2006). Several reports determined that P-glycoprotein expression appears to be higher in more aggressive, locally advanced or metastatic tumors and is associated with a shorter overall survival for tamoxifen-treated patients, suggesting its use as a putative prognostic factor (Schneider et al, 1994;Linn et al, 1995;Tsukamoto et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Endoxifen, the Active Metabolite of Tamoxifen, Is a Substrate of the Efflux Transporter P-Glycoprotein (Multidrug Resistance 1)

Teft¹,

Mansell²,

Kim³

2010

Drug Metab Dispos

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ABSTRACT:Tamoxifen is widely prescribed to patients with estrogen receptor-positive breast cancer, and it is a prodrug that requires bioactivation by cytochrome P450 enzymes CYP2D6 and 3A4 to generate the active metabolite, endoxifen. Large interpatient variability in endoxifen plasma levels has been reported, and polymorphisms in CYP2D6 have been implicated as a major determinant of such variability. However, little is known regarding the role of drug transporters such as P-glycoprotein [multidrug resistance 1 (MDR1), ATP-binding cassette B1 (ABCB1)] to endoxifen disposition and response. Therefore, we determined the ability of P-glycoprotein to transport endoxifen in vitro, using a polarized human P-glycoprotein-overexpressing cell line. Markedly higher transport of endoxifen was observed in the basal-to-apical direction, which was abrogated in the presence of the potent and specific P-glycoprotein inhibitor (2R)-anti-5-{3-[4-(10,11-difluoromethanodibenzo-suber-5-yl)piperazin-1-yl]-2-hydroxypropoxy}quinoline trihydrochloride (LY335979). To validate the in vivo relevance of P-glycoprotein to endoxifen disposition, plasma and tissue concentrations were also determined in Mdr1a-deficient mice after oral administration of endoxifen. Plasma endoxifen levels did not significantly differ between wild-type and Mdr1a-deficient mice. However, brain concentrations of endoxifen were nearly 20-fold higher in Mdr1a-deficient mice compared to wild-type mice. Because Pglycoprotein is highly expressed at the blood-brain barrier and in some breast cancer tumors, variation in expression and function of this transporter may alter central nervous system entry and the attained intracellular concentration in such breast cancer cells and therefore may prove to be of relevance to therapeutic outcome.

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“…[4][5][6] As a results of the interaction of the UFH to this multidrug transporter protein, alterations of the activities of the transmembrane pump system would be induced and as consequence to influence the drugs response. Since MDR mediated by Pgp has been documented in a variety of human cancer cells and in same case, such as in some carcinomas including breast, ovarian, and renal, has been shown to be associated with a poor response to cancer chemotherapy, [7][8][9][10][11][12][13][14][15][16] UFH could be used as chemosensitizer in the clinical setting to inhibit the mechanism of pleiotropic chemoresistance Pgp-mediated and to potentiate chemotherapy. 17,18 In this study, we evaluated the in vitro effects of UFH on the Pgp function and activity using a human breast cancer cell line, such as MDA-MB-231 19 and assessed whether these effects increased the sensitivity of this carcinoma cell type to antineoplastic drugs.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of P-glycoprotein-mediated multidrug resistance by unfractionated heparin: A new potential chemosensitizer for cancer therapy

Angelini

Febbo²,

Ciofani³

et al. 2005

Cancer Biology & Therapy

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Investigation of MRP‐1 protein and MDR‐1 P‐glycoprotein expression in invasive breast cancer: A prognostic study

Cited by 81 publications

References 25 publications

MRP1 but Not MDR1 Is Associated with Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

MRP1 but Not MDR1 Is Associated with Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

Endoxifen, the Active Metabolite of Tamoxifen, Is a Substrate of the Efflux Transporter P-Glycoprotein (Multidrug Resistance 1)

Inhibition of P-glycoprotein-mediated multidrug resistance by unfractionated heparin: A new potential chemosensitizer for cancer therapy

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