scholarly journals NHERF1/EBP50 as a Target for Modulation of MRP Function in HepG2 Cells

2021 ◽  
Vol 14 (3) ◽  
pp. 239
Author(s):  
Atsushi Kawase ◽  
Miho Hirosoko ◽  
Yuka Sugihara ◽  
Yunosuke Koyama ◽  
Ayaka Fukae ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Breast Cancer Resistance Protein ◽  
Scaffold Proteins ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
Erm Proteins ◽  
P Glycoprotein ◽  
Human Liver Cancer ◽  
Resistance Protein ◽  
Peptide Treatment

As increased expression and activities of efflux transporters (ETs) often cause drug resistance in cancers, we tried modulating ET activity in cancer cells, using scaffold proteins such as ezrin/radixin/moesin (ERM) proteins, and Na+/H+ exchanger regulatory factor-1 (NHERF1)/ERM-binding phosphoprotein of 50 kDa (EBP50). To see whether EBP50 modulated ET activities in human liver cancer HepG2 cells, we used EBP50 siRNA and a designed TAT-PDZ1 peptide. The EBP50 knockdown (EBP50KD) cells had significantly higher intracellular accumulations of Rho123 and carboxy-dichlorofluorescein (CDF), but not H33342 (i.e., the respective substrates of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP)), compared with control HepG2, suggesting that EBP50 knockdown in HepG2 cells decreased activity of P-gp and MRP but not BCRP. Treatment with TAT-PDZ1 peptide (>1 pM) resulted in significantly higher CDF accumulation in HepG2 cells, which persisted for ≥180 min after TAT-PDZ1 peptide treatment. These results imply that EBP50 can modulate ET activities. To our knowledge, this is the first report on using a competitive peptide to modulate interactions between MRP and EBP50.

scholarly journals P-Glycoprotein and Breast Cancer Resistance Protein Restrict Apical-to-Basolateral Permeability of Human Brain Endothelium to Amyloid-β

2009 ◽  
Vol 29 (6) ◽  
pp. 1079-1083 ◽  
Author(s):  
Leon M Tai ◽  
A Jane Loughlin ◽  
David K Male ◽  
Ignacio A Romero
Keyword(s):  
Breast Cancer ◽  
Human Brain ◽  
Breast Cancer Resistance Protein ◽  
Amyloid Β ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Resistance Protein ◽  
The Brain

The clearance of amyloid beta (Aβ) from the brain represents a novel therapeutic target for Alzheimer's disease. Conflicting data exist regarding the contribution of adenosine triphosphatebinding cassette transporters to the clearance of Aβ through the blood-brain barrier. Therefore, we investigated whether Aβ could be a substrate for P-glycoprotein (P-gp) and/or for breast cancer resistance protein (BCRP) using a human brain endothelial cell line, hCMEC/D3. Inhibition of P-gp and BCRP increased apical-to-basolateral, but not basolateral-to-apical, permeability of hCMEC/D3 cells to 125l Aβ 1–40. Our in vitro data suggest that P-gp and BCRP might act to prevent the blood-borne Aβ 1–40 from entering the brain.

scholarly journals Brain and Testis Accumulation of Regorafenib is Restricted by Breast Cancer Resistance Protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1)

2015 ◽  
Vol 32 (7) ◽  
pp. 2205-2216 ◽  
Author(s):  
Anita Kort ◽  
Selvi Durmus ◽  
Rolf W. Sparidans ◽  
Els Wagenaar ◽  
Jos H. Beijnen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Resistance Protein

scholarly journals P-Glycoprotein and Breast Cancer Resistance Protein in Canine Inflammatory and Noninflammatory Grade III Mammary Carcinomas

2019 ◽  
Vol 56 (6) ◽  
pp. 840-847 ◽  
Author(s):  
Michela Levi ◽  
Laura Peña ◽  
Angela Alonso-Díez ◽  
Barbara Brunetti ◽  
Luisa Vera Muscatello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
Mammary Carcinomas ◽  
P Glycoprotein ◽  
Response To Chemotherapy ◽  
Inflammatory Phenotype ◽  
Resistance Protein ◽  
Grade Iii

P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) expression are frequently related to multidrug resistance (MDR) in neoplastic cells. Canine inflammatory and grade III noninflammatory mammary carcinomas (IMC and non-IMC) are aggressive tumors that could benefit from chemotherapy. This study describes the immunohistochemical detection of P-gp and BCRP in 20 IMCs and 18 non-IMCs from dogs that had not received chemotherapy. Our aim was to determine if P-gp and BCRP expression was related to the “inflammatory” phenotype, to establish a basis for future studies analyzing the response to chemotherapy in dogs with highly malignant mammary cancer. Immunolabeling was primarily membranous for P-gp with a more intense labeling in emboli, and immunolabeling was membranous and cytoplasmic for BCRP. P-gp was expressed in 17 of 20 (85%) IMCs compared to 7 of 18 (39%) non-IMCs ( P = 0.006). BCRP was expressed within emboli in 15 of 19 (79%) emboli in IMC, 12 of 15 (80%) primary IMCs, and 12 of 18 (67%) non-IMCs, without statistically significant differences ( P > .05). All IMCs and 67% of non-IMCs expressed at least 1 of the 2 transporters, and 63% (12/19) of IMCs and 39% (7/18) of non-IMCs expressed both P-gp and BCRP. P-gp and BCRP evaluation might help select patients for chemotherapy. P-gp, expressed in a significantly higher percentage of IMCs vs non-IMCs, might play a specific role in the chemoresistance of IMC.

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