Evidence for a Role of the Adenosine 5′-Triphosphate-Binding Cassette Transporter A1 in the Externalization of Annexin I from Pituitary Folliculo-Stellate Cells

Annexin 1 (ANXA1) has a well-demonstrated role in early delayed inhibitory feedback of glucocorticoids in the pituitary. ANXA1 is located in folliculo-stellate (FS) cells, and glucocorticoids act on these cells to externalize and stimulate the synthesis of ANXA1. However, ANXA1 lacks a signal sequence so the mechanism by which ANXA1 is externalized from FS cells was unknown and has been investigated. The ATP-binding cassette (ABC) transporters are a large group of transporters with varied roles that include the externalization of proteins. Glucocorticoid-induced externalization of ANXA1 from an FS cell line (TtT/GF) and rat anterior pituitary was blocked by glyburide, which inhibits ABC transporters. Glyburide also blocked the glucocorticoid inhibition of forskolin-stimulated ACTH release from pituitary tissue in vitro. RT-PCR revealed mRNA and Western blotting demonstrated protein for the ATP binding cassette A1 (ABCA1) transporter in mouse FS, TtT/GF, and A549 lung adenocarcinoma cells from which glucocorticoids also induce externalization of ANXA1. In TtT/GF cells, immunofluorescence labeling revealed a near total colocalization of cell surface ANXA1 and ABCA1. We conclude that ANXA1, which mediates the early delayed feedback of glucocorticoids in the anterior pituitary, is externalized from FS cells by an ABC transporter and that the ABCA1 transporter is a likely candidate.

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Expression of ATP binding cassette E1 enhances viability and invasiveness of lung adenocarcinoma cells in vitro

Molecular Medicine Reports ◽

10.3892/mmr.2016.5388 ◽

2016 ◽

Vol 14 (2) ◽

pp. 1345-1350 ◽

Cited By ~ 5

Author(s):

Ye Tian ◽

Xin Tian ◽

Xu Han ◽

Yong Chen ◽

Cheng-Yang Song ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Atp Binding ◽

Adenocarcinoma Cells ◽

Lung Adenocarcinoma Cells ◽

Atp Binding Cassette

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A Selective ATP-Binding Cassette Subfamily G Member 2 Efflux Inhibitor Revealed via High-Throughput Flow Cytometry

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057112456875 ◽

2012 ◽

Vol 18 (1) ◽

pp. 26-38 ◽

Cited By ~ 15

Author(s):

J. Jacob Strouse ◽

Irena Ivnitski-Steele ◽

Hadya M. Khawaja ◽

Dominique Perez ◽

Jerec Ricci ◽

...

Keyword(s):

Molecular Probes ◽

Atp Binding ◽

Specific Substrate ◽

Tumor Resistance ◽

Drug Concentrations ◽

Efflux Inhibition ◽

Substrate Inhibitor ◽

Atp Binding Cassette

Chemotherapeutics tumor resistance is a principal reason for treatment failure, and clinical and experimental data indicate that multidrug transporters such as ATP-binding cassette (ABC) B1 and ABCG2 play a leading role by preventing cytotoxic intracellular drug concentrations. Functional efflux inhibition of existing chemotherapeutics by these pumps continues to present a promising approach for treatment. A contributing factor to the failure of existing inhibitors in clinical applications is limited understanding of specific substrate/inhibitor/pump interactions. We have identified selective efflux inhibitors by profiling multiple ABC transporters against a library of small molecules to find molecular probes to further explore such interactions. In our primary screening protocol using JC-1 as a dual-pump fluorescent reporter substrate, we identified a piperazine-substituted pyrazolo[1,5-a]pyrimidine substructure with promise for selective efflux inhibition. As a result of a focused structure-activity relationship (SAR)–driven chemistry effort, we describe compound 1 (CID44640177), an efflux inhibitor with selectivity toward ABCG2 over ABCB1. Compound 1 is also shown to potentiate the activity of mitoxantrone in vitro as well as preliminarily in vivo in an ABCG2-overexpressing tumor model. At least two analogues significantly reduce tumor size in combination with the chemotherapeutic topotecan. To our knowledge, low nanomolar chemoreversal activity coupled with direct evidence of efflux inhibition for ABCG2 is unprecedented.

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Growth Promotion and Increased ATP-Binding Cassette Transporters Expression by Liraglutide in Triple Negative Breast Cancer Cell Line MDA-MB-231

Drug Research ◽

10.1055/a-1345-7890 ◽

2021 ◽

Author(s):

Amir Shadboorestan ◽

Parastoo Tarighi ◽

Mahsa Koosha ◽

Homa Faghihi ◽

Mohammad Hossein Ghahremani ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Triple Negative Breast Cancer ◽

Abc Transporters ◽

Triple Negative ◽

Epithelial Mesenchymal Transition ◽

Growth Promotion ◽

Atp Binding ◽

Mesenchymal Transition ◽

Atp Binding Cassette

Background Glucagon-like petide-1 (GLP-1) agonists such as liraglutide are widely employed in type 2 diabetes due to their glucose reducing properties and small risk of hypoglycemia. Recently, it has been shown that GLP-1agonists can inhibit breast cancer cells growth. Nonetheless, concerns are remained about liraglutide tumor promoting effects as stated by population studies. Material and Methods We evaluated the effects liraglutide on proliferation of MDA-MB-231 cells by MTT assay and then ATP-binding cassette (ABC) transporters expressions assessed by Real time PCR. Statistical comparisons were made using one-way analysis of variance followed by a post hoc Dunnett test. Results Here, we report that liraglutide can stimulate the growth of highly invasive triple negative cell line MDA-MB-231; which can be attributed to AMPK-dependent epithelial-mesenchymal transition (EMT) happening in MDA-MB-231 context. Toxicity effects were only observed with concentrations far above the serum liraglutide concentration. ATP-binding cassette (ABC) transporters expressions were upregulated, indicating the possible drug resistance and increased EMT. Conclusion In conclusion, these results suggest that liraglutide should be used with caution in patients who are suffering or have the personal history of triple negative breast cancer. However, more detailed studies are required to deepen understanding of liraglutide consequences in triple negative breast cancer. ▶Graphical Abstract.

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Genome-wide analysis of ATP-binding cassette (ABC) transporters in the sweetpotato whitefly, Bemisia tabaci

BMC Genomics ◽

10.1186/s12864-017-3706-6 ◽

2017 ◽

Vol 18 (1) ◽

Cited By ~ 25

Author(s):

Lixia Tian ◽

Tianxue Song ◽

Rongjun He ◽

Yang Zeng ◽

Wen Xie ◽

...

Keyword(s):

Bemisia Tabaci ◽

Abc Transporters ◽

Atp Binding ◽

Sweetpotato Whitefly ◽

Genome Wide Analysis ◽

Genome Wide ◽

Atp Binding Cassette

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Endocrine Disruptors Differentially Target ATP-Binding Cassette Transporters in the Blood-Testis Barrier and Affect Leydig Cell Testosterone Secretion In Vitro

Toxicological Sciences ◽

10.1093/toxsci/kft198 ◽

2013 ◽

Vol 136 (2) ◽

pp. 382-391 ◽

Cited By ~ 52

Author(s):

Anita C. A. Dankers ◽

Maarke J. E. Roelofs ◽

Aldert H. Piersma ◽

Fred C. G. J. Sweep ◽

Frans G. M. Russel ◽

...

Keyword(s):

Endocrine Disruptors ◽

Leydig Cell ◽

Atp Binding ◽

Testosterone Secretion ◽

Atp Binding Cassette Transporters ◽

Blood Testis Barrier ◽

Atp Binding Cassette

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Correction to: ATP binding cassette (ABC) transporters: expression and clinical value in glioblastoma

Journal of Neuro-Oncology ◽

10.1007/s11060-018-2830-8 ◽

2018 ◽

Vol 138 (3) ◽

pp. 487-487

Author(s):

Antonin Dréan ◽

Shai Rosenberg ◽

François-Xavier Lejeune ◽

Larissa Goli ◽

Aravindan Arun Nadaradjane ◽

...

Keyword(s):

Abc Transporters ◽

Atp Binding ◽

Clinical Value ◽

Atp Binding Cassette

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Expression of some ATP-binding cassette transporters in acute myeloid leukemia

Hematology Reports ◽

10.4081/hr.2017.7406 ◽

2017 ◽

Vol 9 (4) ◽

Cited By ~ 5

Author(s):

Antonella Maria Salvia ◽

Flavia Cuviello ◽

Sabrina Coluzzi ◽

Roberta Nuccorini ◽

Immacolata Attolico ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Abc Transporters ◽

Healthy Subjects ◽

Myeloid Leukemia ◽

Resistance Mechanisms ◽

Atp Binding ◽

Atp Binding Cassette Transporters ◽

Acute Myeloid ◽

Atp Binding Cassette

Hematopoietic cells express ATP binding cassette (ABC) transporters in relation to different degrees of differentiation. One of the known multidrug resistance mechanisms in acute myeloid leukemia (AML) is the overexpression of efflux pumps belonging to the superfamily of ABC transporters such as ABCB1, ABCG2 and ABCC1. Although several studies were carried out to correlate ABC transporters expression with drug resistance, little is known about their role as markers of diagnosis and progression of the disease. For this purpose we investigated the expression, by real-time PCR, of some ABC genes in bone marrow samples of AML patients at diagnosis and after induction therapy. At diagnosis, ABCG2 was always down-regulated, while an up regulated trend for ABCC1 was observed. After therapy the examined genes showed a different expression trend and approached the values of healthy subjects suggesting that this event could be considered as a marker of AML regression. The expression levels of some ABC transporters such as ABCC6, seems to be related to gender, age and to the presence of FLT3/ITD gene mutation.

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Stickleback embryos use ATP-binding cassette transporters as a buffer against exposure to maternally derived cortisol

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2015.2838 ◽

2016 ◽

Vol 283 (1826) ◽

pp. 20152838 ◽

Cited By ~ 17

Author(s):

Ryan T. Paitz ◽

Syed Abbas Bukhari ◽

Alison M. Bell

Keyword(s):

Abc Transporters ◽

Gasterosteus Aculeatus ◽

Transcriptional Response ◽

Threespine Stickleback ◽

Egg Laying ◽

Atp Binding ◽

Active Efflux ◽

Atp Binding Cassette Transporters ◽

Stress Influences ◽

Atp Binding Cassette

Offspring from females that experience stressful conditions during reproduction often exhibit altered phenotypes and many of these effects are thought to arise owing to increased exposure to maternal glucocorticoids. While embryos of placental vertebrates are known to regulate exposure to maternal glucocorticoids via placental steroid metabolism, much less is known about how and whether egg-laying vertebrates can control their steroid environment during embryonic development. We tested the hypothesis that threespine stickleback ( Gasterosteus aculeatus ) embryos can regulate exposure to maternal steroids via active efflux of maternal steroids from the egg. Embryos rapidly (within 72 h) cleared intact steroids, but blocking ATP-binding cassette (ABC) transporters inhibited cortisol clearance. Remarkably, this efflux of cortisol was sufficient to prevent a transcriptional response of embryos to exogenous cortisol. Taken together, these findings suggest that, much like their placental counterparts, developing fish embryos can actively regulate their exposure to maternal cortisol. These findings highlight the fact that even in egg-laying vertebrates, the realized exposure to maternal steroids is mediated by both maternal and embryonic processes and this has important implications for understanding how maternal stress influences offspring development.

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