ArticleOncogene2002
Induction of human MDR1 gene expression by 2-acetylaminofluorene is mediated by effectors of the phosphoinositide 3-kinase pathway that activate NF-kappaB signaling.
Article in Oncogene, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 191 citations in OpenAlex.
- Association between ABCB1 (3435C>T) polymorphism and susceptibility of colorectal cancer: A meta-analysis.Medicine · 2020Pooled it
- Understanding and overcoming multidrug resistance in cancer.Nature reviews. Clinical oncology · 2025Review
- ERα36 PromotesInternational journal of molecular sciences · 2025Article
- Intracellular TAS2Rs act as a gatekeeper for the excretion of harmful substances via ABCB1 in keratinocytes.FASEB bioAdvances · 2024Article
- Impact of Combination Therapy with Chemical Drugs and Megavoltage X-ray Exposure on Breast Cancer Stem Cells' Viability and Proliferation of MCF-7 and MDA-MB-231 Cell Lines.Current pharmaceutical design · 2024Article
- Fibrous stroma: Driver and passenger in cancer development.Science signaling · 2022Review
- Nek2 Kinase Signaling in Malaria, Bone, Immune and Kidney Disorders to Metastatic Cancers and Drug Resistance: Progress on Nek2 Inhibitor Development.Molecules (Basel, Switzerland) · 2022Review
- α-Mangostin Nanoparticles Cytotoxicity and Cell Death Modalities in Breast Cancer Cell Lines.Molecules (Basel, Switzerland) · 2021Review
- Differential sensitivity of renal carcinoma cells to doxorubicin and epigenetic therapeutics depends on the genetic background.Molecular and cellular biochemistry · 2021Article
- Impact of Local Liver Irradiation Concurrent Versus Sequential with Lenvatinib on Pharmacokinetics and Biodistribution.Cancers · 2021Article
- Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation.Pharmaceutics · 2021Article
- Short-chain fatty acids exert opposite effects on the expression and function of p-glycoprotein and breast cancer resistance protein in rat intestine.Acta pharmacologica Sinica · 2021Article
- Regulation of ABC Drug Efflux Transporters in Human T-Cells Exposed to an HIV Pseudotype.Frontiers in pharmacology · 2021Article
- Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Possible Susceptibility Genes for Intervention against Chemotherapy-Induced Cardiotoxicity.Oxidative medicine and cellular longevity · 2020Review
- MARK2 enhances cisplatin resistance via PI3K/AKT/NF-κB signaling pathway in osteosarcoma cells.American journal of translational research · 2020Article
- Nek2B activates the wnt pathway and promotes triple-negative breast cancer chemothezrapy-resistance by stabilizing β-catenin.Journal of experimental & clinical cancer research : CR · 2019Article
- Acid ceramidase promotes drug resistance in acute myeloid leukemia through NF-κB-dependent P-glycoprotein upregulation.Journal of lipid research · 2019Article
- Optimal control nodes in disease-perturbed networks as targets for combination therapy.Nature communications · 2019Article
- Obesity-Altered Adipose Stem Cells Promote ER⁺ Breast Cancer Metastasis through Estrogen Independent Pathways.International journal of molecular sciences · 2019Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The expression of P-glycoprotein encoded by the multidrug resistance (MDR1) gene is associated with the emergence of the MDR phenotype in cancer cells. Human MDR1 and its rodent homolog mdr1a and mdr1b are frequently overexpressed in liver cancers. However, the underlying mechanisms are largely unknown. The hepatocarcinogen 2-acetylaminofluorene (2-AAF) efficiently activates rat mdr1b expression in cultured cells and in Fisher 344 rats. We recently reported that activation of rat mdr1b in cultured cells by 2-AAF involves a cis-activating element containing a NF-kappaB binding site located -167 to -158 of the rat mdr1b promoter. 2-AAF activates IkappaB kinase (IKK), resulting in degradation of IkappaBbeta and activation of NF-kappaB. In this study, we report that 2-AAF could also activate the human MDR1 gene in human hepatoma and embryonic fibroblast 293 cells. Induction of MDR1 by AAF was mediated by DNA sequence located at -6092 which contains a NF-kappaB binding site. Treating hepatoma cells with 2-AAF activated phosphoinositide 3-kinase (PI3K) and its downstream effectors Rac1, and NAD(P)H oxidase. Transient transfection assays demonstrated that constitutively activated PI3K and Rac1 enhanced the activation of the MDR1 promoter by 2-AAF. Treatment of hepatoma cells with 2-AAF also activated another PI3K downstream effector Akt. Transfection of recombinant encoding a dominant activated Akt also enhanced the activation of MDR1 promoter activation by 2-AAF. These results demonstrated that 2-AAF up-regulates MDR1 expression is mediated by the multiple effectors of the PI3K signaling pathway.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.