ABCC10 (ATP-binding cassette, sub-family C (CFTR/MRP), member 10)
2014-04-01 Elizabeth Hopper-Borge  , Natalya Domanitskaya   AffiliationFox Chase Cancer Center, Developmental Therapeutics Program, Philadelphia, PA, USA
Identity
DNA/RNA
Note
Description
Transcription
In normal tissue
A study of the ABCC10 promoter revealed that the presence of E2F and Sp1 sites are required for maximum transcription. In addition other elements were found in the promoter including: cAMP-responsive element binding protein, estrogen receptor binding site, hepatic nuclear factor, progesterone receptor binding site, and sterol regulatory element binding protein (Dabrowska and Sirotnak, 2004).
ABCC10 transcript is widespread at low levels (Hopper et al., 2001; Maher et al., 2005) with highest expression in the pancreas. Decreased expression is observed in activated resting T and B cells (Takayanagi et al., 2004).
In cancer
In cell lines: In terms of cancer, the ABCC10 gene is expressed in human tumor cell lines, HepG2, CWR22RV1 and TSU-PR1 at greater or equal levels than ABCC1, ABCC2 and ABCC3. Novel ABCC10 transcripts have been identified in HepG2, and CWR22RV1 cells. These transcripts are heterogeneic and imply complexity in the exons and introns of this region (Dabrowska and Sirotnak, 2004).
In breast cancer: ABCC10 transcript is upregulated in breast tumors treated with 5-fluorouracil, anthracycline, cyclophosphamide or taxane based neoadjuvant chemotherapy in comparison with normal tissue. Further, ABCC10 transcript expression is associated with ER positive breast cancer (Hlavac et al., 2013).
In acute myeloid leukemia: ABCC10 transcript is also expressed in acute myeloid leukemia (Hu et al., 2011).
In hepatocellular carcinoma: Transcripts from ABCC10 and various other transporters including: ABCB6, ABCC1, ABCC4, ABCC5, and ABCC12 are upregulated in over 50% hepatocellular carcinoma in untreated patients. It was also observed that microRNA let-7a/e is able to downregulate ABCC10 transcript (Borel et al., 2012).
Proteins

Description
ABCC10, like ABCC1, 2, 3 and 6 (see figure above A) has an N-terminal membrane spanning domain (MSD) that is not present in ABCC4, 5, 11 or 12 (figure above B). All ABCC subfamily members contain two Nucleotide Binding Domains (NBD).
Expression
ABCC10 is expressed in cell lines derived from acute myeloid leukemia (Hu et al., 2011).
Localisation
Function
ABCC10 transports estrogen β glucuronide, and exhibits modest transport of leukotrienes. Similar to other subfamily members ABCC10 can efflux lipophilic anions (Chen et al., 2003).
ABCC10 is a drug efflux pump that is able to mediate transport of taxanes in vivo. In vitro studies have shown that ABCC10 confers resistance to a variety of hydrophobic drugs, including paclitaxel, docetaxel, vincristine, vinblastine, epothilone B, cytarabine, in a glutathione independent manner (Hopper-Borge et al., 2004; Hopper-Borge et al., 2009)
Prior work has shown that ABCC10 may have a role in natural killer cell mediated lysis. A report demonstrated that a peptide derived from ABCC10 binds to HLA-E and inhibits NK cell-mediated lysis in a CD94 and class I-dependent fashion (Wooden et al., 2005).
ABCC10 ATPase activity is stimulated by estradiol glucuronide, leukotriene, tamoxifen, docetaxel and ARA-C (Malofeeva et al., 2012).
In vivo
Abcc10 protects thymus, spleen and bone marrow when exposed to paclitaxel in vivo. Abcc10 loss promotes loss of white blood cells, increased weight loss and increased lethality in mice exposed to high doses of paclitaxel (Hopper-Borge et al., 2011).
Homology
ABCC10 is present in many species including: drosophila melanogaster, xenopus, saccharomyces cerevisiae, danio rerio, sus scrofa, mus musculus, latimeria chalumnae, felis catus, bos taurus, tetranychus urticae (Schippert et al., 2008; Dermauw et al., 2013). ABCC10 is present in all placental mammals, similar to other subfamily members, ABCC1, ABCC3, ABCC4-7, and ABCC9 (Moitra and Dean, 2011).
Implicated in
ABCC10 is overexpressed in NSCLC. The expression of ABCC10 in adenocarcinoma is higher than in squamous cell carcinoma. ABCC10 expression in adenocarcinoma correlates with pathological grades and TNM stages (Wang et al., 2009).
ABCC10 expression may confer therapeutic resistance in solid breast tumors (submitted, Domanitskaya et al.).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 19082471 | 2009 | ABCC10/MRP7 is associated with vinorelbine resistance in non-small cell lung cancer. | Bessho Y et al |
| 22314424 | 2012 | Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma. | Borel F et al |
| 23979916 | 2013 | Expression of efflux transporters in human ocular tissues. | Chen P et al |
| 12527806 | 2003 | Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). | Chen ZS et al |
| 15474296 | 2004 | Regulation of transcription of the human MRP7 gene. Characteristics of the basal promoter and identification of tumor-derived transcripts encoding additional 5' end heterogeneity. | Dabrowska M et al |
| 21551263 | 2011 | Chemotherapy dosing schedule influences drug resistance development in ovarian cancer. | De Souza R et al |
| 23663308 | 2013 | A burst of ABC genes in the genome of the polyphagous spider mite Tetranychus urticae. | Dermauw W et al |
| 24067562 | 2013 | Tenofovir-induced renal tubular dysfunction in vertically HIV-infected patients associated with polymorphisms in ABCC2, ABCC4 and ABCC10 genes. | Giacomet V et al |
| 20603432 | 2011 | Circulating tumor cells (CTCs) in metastatic breast cancer (MBC): prognosis, drug resistance and phenotypic characterization. | Gradilone A et al |
| 23556449 | 2013 | The expression profile of ATP-binding cassette transporter genes in breast carcinoma. | Hlaváč V et al |
| 22294766 | 2012 | The role of ABC transporters in progression and clinical outcome of colorectal cancer. | Hlavata I et al |
| 11146224 | 2001 | Analysis of the structure and expression pattern of MRP7 (ABCC10), a new member of the MRP subfamily. | Hopper E et al |
| 21576088 | 2011 | Contribution of Abcc10 (Mrp7) to in vivo paclitaxel resistance as assessed in Abcc10(-/-) mice. | Hopper-Borge EA et al |
| 21487100 | 2011 | Activity of the multikinase inhibitor sorafenib in combination with cytarabine in acute myeloid leukemia. | Hu S et al |
| 21152861 | 2011 | Isolation and characterization of gemcitabine-resistant human non-small cell lung cancer A549 cells. | Ikeda R et al |
| 12566991 | 2003 | Genomic structure, gene expression, and promoter analysis of human multidrug resistance-associated protein 7. | Kao HH et al |
| 22082652 | 2012 | Association of ABCC10 polymorphisms with nevirapine plasma concentrations in the German Competence Network for HIV/AIDS. | Liptrott NJ et al |
| 15802388 | 2005 | Tissue distribution and hepatic and renal ontogeny of the multidrug resistance-associated protein (Mrp) family in mice. | Maher JM et al |
| 23087055 | 2012 | Modulation of the ATPase and transport activities of broad-acting multidrug resistance factor ABCC10 (MRP7). | Malofeeva EV et al |
| 21194360 | 2011 | Evolution of ABC transporters by gene duplication and their role in human disease. | Moitra K et al |
| 17203221 | 2007 | Multidrug resistance-associated protein 7 expression is involved in cross-resistance to docetaxel in salivary gland adenocarcinoma cell lines. | Naramoto H et al |
| 18445659 | 2008 | MRP7/ABCC10 expression is a predictive biomarker for the resistance to paclitaxel in non-small cell lung cancer. | Oguri T et al |
| 21628669 | 2011 | Genetic variants of ABCC10, a novel tenofovir transporter, are associated with kidney tubular dysfunction. | Pushpakom SP et al |
| 18769560 | 2008 | Microarray analysis of retinal gene expression in chicks during imposed myopic defocus. | Schippert R et al |
| 16857811 | 2006 | ABCA3 as a possible cause of drug resistance in childhood acute myeloid leukemia. | Steinbach D et al |
| 19059376 | 2009 | The high turnover Drosophila multidrug resistance-associated protein shares the biochemical features of its human orthologues. | Szeri F et al |
| 15724843 | 2004 | Human ATP-binding cassette transporter ABCC10: expression profile and p53-dependent upregulation. | Takayanagi S et al |
| 24266639 | 2014 | The putative multidrug resistance protein MRP-7 inhibits methylmercury-associated animal toxicity and dopaminergic neurodegeneration in Caenorhabditis elegans. | VanDuyn N et al |
| 20719174 | 2009 | [Expression and Clinical Significance of ABCC10 in the Patients with Non-small Cell Lung Cancer.]. | Wang P et al |
| 16034073 | 2005 | Cutting edge: HLA-E binds a peptide derived from the ATP-binding cassette transporter multidrug resistance-associated protein 7 and inhibits NK cell-mediated lysis. | Wooden SL et al |
Other Information
Locus ID:
NCBI: 89845
MIM: 612509
HGNC: 52
Ensembl: ENSG00000124574
Variants:
dbSNP: 89845
ClinVar: 89845
TCGA: ENSG00000124574
COSMIC: ABCC10
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA10204 | tenofovir | Chemical | ClinicalAnnotation, Pathway | associated | PD | 21628669 | |
| PA447230 | HIV | Disease | ClinicalAnnotation | associated | PK | PD | 22082652 |
| PA450616 | nevirapine | Chemical | ClinicalAnnotation | associated | PK | PD | 22082652 |
| PA451879 | vincristine | Chemical | Pathway | associated |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36297086 | 2022 | ATP-Binding Cassette Transporter Family C Protein 10 Participates in the Synthesis and Efflux of Hexosylceramides in Liver Cells. | 3 |
| 36297086 | 2022 | ATP-Binding Cassette Transporter Family C Protein 10 Participates in the Synthesis and Efflux of Hexosylceramides in Liver Cells. | 3 |
| 33563765 | 2021 | Exosomal Delivery of FTO Confers Gefitinib Resistance to Recipient Cells through ABCC10 Regulation in an m6A-dependent Manner. | 19 |
| 33563765 | 2021 | Exosomal Delivery of FTO Confers Gefitinib Resistance to Recipient Cells through ABCC10 Regulation in an m6A-dependent Manner. | 19 |
| 30890141 | 2019 | Genetic variation in the ATP binding cassette transporter ABCC10 is associated with neutropenia for docetaxel in Japanese lung cancer patients cohort. | 8 |
| 30890141 | 2019 | Genetic variation in the ATP binding cassette transporter ABCC10 is associated with neutropenia for docetaxel in Japanese lung cancer patients cohort. | 8 |
| 28051999 | 2017 | FOXM1 evokes 5-fluorouracil resistance in colorectal cancer depending on ABCC10. | 35 |
| 28612064 | 2017 | E2F site in the essential promoter region does not confer S phase-specific transcription of the ABCC10 gene in human prostate cancer cells. | 1 |
| 28051999 | 2017 | FOXM1 evokes 5-fluorouracil resistance in colorectal cancer depending on ABCC10. | 35 |
| 28612064 | 2017 | E2F site in the essential promoter region does not confer S phase-specific transcription of the ABCC10 gene in human prostate cancer cells. | 1 |
| 26655271 | 2016 | BAG3-mediated miRNA let-7g and let-7i inhibit proliferation and enhance apoptosis of human esophageal carcinoma cells by targeting the drug transporter ABCC10. | 27 |
| 27468921 | 2016 | Protein expression of ATP-binding cassette transporters ABCC10 and ABCC11 associates with survival of colorectal cancer patients. | 9 |
| 26655271 | 2016 | BAG3-mediated miRNA let-7g and let-7i inhibit proliferation and enhance apoptosis of human esophageal carcinoma cells by targeting the drug transporter ABCC10. | 27 |
| 27468921 | 2016 | Protein expression of ATP-binding cassette transporters ABCC10 and ABCC11 associates with survival of colorectal cancer patients. | 9 |
| 24431074 | 2014 | Masitinib antagonizes ATP-binding cassette subfamily C member 10-mediated paclitaxel resistance: a preclinical study. | 17 |
Citation
Elizabeth Hopper-Borge ; Natalya Domanitskaya
ABCC10 (ATP-binding cassette, sub-family C (CFTR/MRP), member 10)
Atlas Genet Cytogenet Oncol Haematol. 2014-04-01
Online version: http://atlasgeneticsoncology.org/gene/47655/gene-explorer/deep-insight-explorer/
