Single amino acid substitutions in the transmembrane domains of breast cancer resistance protein (BCRP) alter cross resistance patterns in transfectants

2003 ◽  
Vol 107 (5) ◽  
pp. 757-763 ◽  
Author(s):  
Miyu Miwa ◽  
Satomi Tsukahara ◽  
Etsuko Ishikawa ◽  
Sakiyo Asada ◽  
Yasuo Imai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acid ◽  
Breast Cancer Resistance Protein ◽  
Transmembrane Domains ◽  
Single Amino Acid ◽  
Cross Resistance ◽  
Amino Acid Substitutions ◽  
Cancer Resistance ◽  
Resistance Patterns ◽  
Resistance Protein

scholarly journals Chromones bearing amino acid residues: Easily accessible and potent inhibitors of the breast cancer resistance protein ABCG2

2020 ◽  
Vol 202 ◽  
pp. 112503 ◽  
Author(s):  
Emile Roussel ◽  
Alexis Moréno ◽  
Nicolas Altounian ◽  
Christian Philouze ◽  
Basile Pérès ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acid ◽  
Breast Cancer Resistance Protein ◽  
Amino Acid Residues ◽  
Cancer Resistance ◽  
Resistance Protein

scholarly journals Development of Conformation Independent Computational Models for the Early Recognition of Breast Cancer Resistance Protein Substrates

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Melisa Edith Gantner ◽  
Mauricio Emiliano Di Ianni ◽  
María Esperanza Ruiz ◽  
Alan Talevi ◽  
Luis E. Bruno-Blanch
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Oral Absorption ◽  
Early Recognition ◽  
Machine Learning Algorithms ◽  
Oral Drug ◽  
Cross Resistance ◽  
Cancer Resistance ◽  
Linear Discriminant ◽  
Resistance Protein

ABC efflux transporters are polyspecific members of the ABC superfamily that, acting as drug and metabolite carriers, provide a biochemical barrier against drug penetration and contribute to detoxification. Their overexpression is linked to multidrug resistance issues in a diversity of diseases. Breast cancer resistance protein (BCRP) is the most expressed ABC efflux transporter throughout the intestine and the blood-brain barrier, limiting oral absorption and brain bioavailability of its substrates. Early recognition of BCRP substrates is thus essential to optimize oral drug absorption, design of novel therapeutics for central nervous system conditions, and overcome BCRP-mediated cross-resistance issues. We present the development of an ensemble of ligand-based machine learning algorithms for the early recognition of BCRP substrates, from a database of 262 substrates and nonsubstrates compiled from the literature. Such dataset was rationally partitioned into training and test sets by application of a 2-step clustering procedure. The models were developed through application of linear discriminant analysis to random subsamples of Dragon molecular descriptors. Simple data fusion and statistical comparison of partial areas under the curve of ROC curves were applied to obtain the best 2-model combination, which presented 82% and 74.5% of overall accuracy in the training and test set, respectively.

Breast Cancer Resistance Protein: A Potential Therapeutic Target for Cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Sonali Mehendale-Munj
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Protein A ◽  
The Body ◽  
Cancer Therapies ◽  
Cancer Resistance ◽  
Lung Cancers ◽  
Resistance Protein ◽  
Atp Regulation ◽  
Treatment Procedures

: Breast Cancer Resistance Protein (BCRP) is an efflux transporter responsible for causing multidrug re-sistance(MDR). It is known to expel many potent antineoplastic drugs, owing to its efflux function. Efflux of chemothera-peutics because of BCRP develops resistance to manydrugs, leading to failure in cancer treatment. BCRP plays an important role in physiology by protecting the organism from xenobiotics and other toxins. It is a half-transporter affiliated to theATP-binding cassette (ABC) superfamily of transporters, encoded by the gene ABCG2 and functions in response to adenosine triphosphate (ATP). Regulation of BCRP expression is critically controlled at molecular levels which help in maintaining the balance of xenobiotics and nutrients inside the body. Expression of BCRP can be found in brain, liver, lung cancers and acute myeloid leukemia (AML). Moreover, it is also expressed at high levels in stem cells and many cell lines. This frequent expression of BCRP has an impact on the treatment procedures and if not scrutinized may lead to failure of many cancer therapies.

scholarly journals Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP)

2021 ◽  
Vol 22 (11) ◽  
pp. 5534
Author(s):  
Elin Engdahl ◽  
Maarten van Schijndel ◽  
Dimitrios Voulgaris ◽  
Michela Di Criscio ◽  
Kerry Ramsbottom ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bisphenol A ◽  
Blood Brain Barrier ◽  
Breast Cancer Resistance Protein ◽  
Brain Barrier ◽  
Production Volume ◽  
Cancer Resistance ◽  
Blood Brain ◽  
Resistance Protein

The breast cancer resistance protein (BCRP) is an important efflux transporter in the blood-brain barrier (BBB), protecting the brain from a wide range of substances. In this study, we investigated if BCRP function is affected by bisphenol A (BPA), a high production volume chemical used in common consumer products, as well as by bisphenol F (BPF) and bisphenol S (BPS), which are used to substitute BPA. We employed a transwell-based in vitro cell model of iPSC-derived brain microvascular endothelial cells, where BCRP function was assessed by measuring the intracellular accumulation of its substrate Hoechst 33342. Additionally, we used in silico modelling to predict if the bisphenols could directly interact with BCRP. Our results showed that BPA significantly inhibits the transport function of BCRP. Additionally, BPA was predicted to bind to the cavity that is targeted by known BCRP inhibitors. Taken together, our findings demonstrate that BPA inhibits BCRP function in vitro, probably by direct interaction with the transporter. This effect might contribute to BPA’s known impact on neurodevelopment.

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