ABCC10 Antibody
Description
2.1. Role in Drug Resistance
ABCC10 antibodies have been instrumental in identifying the protein's contribution to chemoresistance:
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Gefitinib Resistance: In non-small cell lung cancer (NSCLC), ABCC10 overexpression reduces intracellular gefitinib accumulation by ~25%, correlating with drug resistance. Knockdown of ABCC10 via siRNA restores sensitivity, as shown by reduced IC₅₀ values (38.5% decrease) and increased apoptosis .
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Taxane Resistance: ABCC10 confers resistance to paclitaxel and docetaxel in vitro (116- and 46-fold resistance, respectively). Abcc10⁻/⁻ mice exhibit hypersensitivity to paclitaxel, with severe bone marrow toxicity, confirming ABCC10's role in intrinsic drug resistance .
2.2. Metabolic Regulation
ABCC10 antibodies revealed its role in lipid metabolism:
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In Abcc10⁻/⁻ mice, plasma and intestinal triglycerides decreased by ~38% and ~36%, respectively. Hepatic lipid droplet accumulation was reduced by 59% in high-fat diet-fed mice, indicating ABCC10's role in dietary fat absorption .
2.3. Cancer Pathogenesis
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Breast Cancer: ABCC10 expression correlates with HER2+/ER+ status in breast cancer cell lines (e.g., MCF7, T47D). Triple-negative subtypes show heterogeneous ABCC10 expression, with 38.9% of tumors lacking detectable protein .
3.1. Mechanism of Action
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ABCC10 actively effluxes substrates like gefitinib (efflux ratio = 7.8) and glucuronide conjugates (e.g., estradiol-17-beta-glucuronide) via ATP-dependent transport .
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Inhibition by cepharanthine reverses ABCC10-mediated drug resistance, restoring intracellular drug levels .
3.2. Tissue-Specific Expression
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Normal Tissues: High expression in testes, liver, and kidneys .
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Tumors: Overexpressed in NSCLC, breast, and pancreatic cancers, with transcript levels elevated in 70% of NSCLC cell lines .
Technical Considerations
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Western Blotting: Use RIPA buffer for membrane protein extraction. Note potential discrepancies between predicted (161 kDa) and observed (~29 kDa) molecular weights due to proteolytic cleavage .
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IHC Optimization: Antigen retrieval with citrate buffer (pH 6.0) recommended for FFPE tissues .
Clinical Implications
ABCC10 is a potential biomarker for predicting chemoresistance and a therapeutic target. Inhibitors like cepharanthine or tyrosine kinase inhibitors (e.g., nilotinib) may enhance drug efficacy in ABCC10-overexpressing tumors .
Product Specs
Target Background
Q&A
Basic Research Questions
What experimental approaches validate ABCC10 antibody specificity in membrane protein studies?
To confirm antibody specificity:
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Perform knockdown/overexpression models with parallel Western blot analysis comparing parental vs modified cell lines (e.g., 2.4-fold IC50 increase in ABCC10-overexpressing H292 cells )
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Combine immunofluorescence colocalization with organelle markers (e.g., lysosomal Lysotracker Deep Red )
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Validate using orthogonal methods like qRT-PCR for mRNA-correlated protein expression (P<0.01 significance in resistant NSCLC lines )
How does ABCC10 antibody selection impact chemoresistance study design?
Critical considerations include:
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Epitope mapping: C-terminal vs N-terminal antibodies affect detection of truncation variants
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Post-translational modifications: Phospho-specific antibodies required for studying regulatory mechanisms (e.g., ATPase activity modulation )
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Cross-reactivity screening: Essential due to 65% homology between ABCC10 and ABCC1 in nucleotide-binding domains
What controls are essential for ABCC10 functional assays?
Advanced Research Challenges
How to resolve contradictory data on ABCC10's role in taxane vs gefitinib resistance?
Mechanistic reconciliation strategies:
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Substrate competition assays: Test simultaneous transport of [³H]-paclitaxel vs gefitinib (7.8 efflux ratio observed for gefitinib )
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Structural modeling: Compare drug-binding pockets using cryo-EM data of ABC transporter homologs
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Pathway analysis: Integrate RNA-seq data with phosphoproteomics to identify EGFR-ABCC10 crosstalk
What advanced models address ABCC10's lysosomal vs plasma membrane localization?
6. Methodological framework for analyzing ABCC10-mediated multidrug resistance (MDR):
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Quantitative transport profiling:
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Dynamic ATPase monitoring:
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Single-cell resolution analysis:
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Combine antibody-based imaging with RNAscope® for protein:mRNA correlation
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Critical Data Interpretation Guidelines
7. Addressing ABCC10 antibody variability across cancer types:
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Tissue-specific glycosylation: Perform PNGase F treatment before Western blot
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Stoichiometric calibration: Use recombinant ABCC10 protein standards (0.1-2 μg loading range )
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Multiplex validation: Triple SILAC quantification with parallel reaction monitoring MS
8. Statistical considerations for preclinical ABCC10 studies:
