p-Anilinoaniline Enhancement of Dioxin-Induced CYP1A1 Transcription and Aryl Hydrocarbon Receptor Occupancy of CYP1A1 Promoter: Role of the Cell Cycle

Elliott, Althea A.; Joiakim, Aby; Mathieu, Patricia; Duniec-Dmuchowski, Zofia; Kocarek, Thomas A.; Reiners, John J.

doi:10.1124/dmd.111.042549

Cited by 2 publications

(4 citation statements)

References 45 publications

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“…The activated AhR, in addition to effecting CYP1A1 transcription, also induces CYP1A2 transcription in MCF10A cells (Elliott et al, 2012). Pretreatment of MCF10A cultures with 500 nM gefitinib or AG1478, concentrations sufficient to suppress EGFR phosphorylation, dramatically increased the accumulation of CYP1A2 mRNA in TCDD-treated cultures (Fig.…”

Section: Egfr Inhibitor Modulation Of Egfr and Extracellularmentioning

confidence: 89%

“…The procedures used for the preparation of cell extracts and Western blot analyses have been described in detail (Reiners et al, 1998;Elliott et al, 2012), with the exception that lysates were prepared in radioimmunoprecipitation assay lysis buffer supplemented with Halt phosphatase and protease inhibitor cocktails. Murine monoclonal antibodies to phospho-EGFR (Tyr1068; dilution 1:2000), a rabbit monoclonal antibody to human GAPDH (product no.…”

Section: Methodsmentioning

confidence: 99%

“…The procedures used for the isolation and analyses of CYP1A1 hnRNA have been described in detail (Elliott et al, 2012). For analyses, we used PCR primers that amplified a 120-base pair sequence corresponding to a region spanning the first exon-intron of human CYP1A1.…”

Section: Methodsmentioning

confidence: 99%

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Epidermal Growth Factor Receptor Kinase Inhibitors Synergize with TCDD to Induce CYP1A1/1A2 in Human Breast Epithelial MCF10A Cells

Joiakim

Mathieu

Shelp

et al. 2016

Drug Metabolism and Disposition

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CYP1A1 and CYP1A2 are transcriptionally activated in the human normal breast epithelial cell line MCF10A following exposure to 2,3,7,. Shifting MCF10A cultures to medium deficient in serum and epidermal growth factor (EGF) caused rapid reductions in the activated (i.e., phosphorylated) forms of extracellular regulated kinases (ERKs) and the epidermal growth factor receptor (EGFR). Shifting to serum/EGF-deficient medium also enhanced TCDDmediated induction of cytochrome P450 (CYP)1A1. Treatment of cells cultured in complete medium with the EGFR inhibitors gefitinib (Iressa), AG1478, and CI-1033 resulted in concentration-dependent reductions of active EGFR and ERKs, and increased CYP1A1 mRNA content ∼3-to 18-fold above basal level. EGFR inhibitors synergized with TCDD and resulted in transient CYP1A1 and CYP1A2 mRNA accumulations ∼8-fold greater (maximum at 5 hours) than that achieved with only TCDD. AG1478, gefitinib, and TCDD individually induced small increases (∼1.2-to 2.5-fold) in CYP1A1 protein content but did not cause additive or synergistic accumulations of CYP1A1 protein when used in combination. The mitogen-activated protein kinase kinase inhibitor PD184352 inhibited ERK and EGFR activation in a concentration-dependent fashion without causing CYP1A1 mRNA accumulation. However, cotreatment with PD184352 potentiated TCDD-mediated CYP1A1 induction. TCDD-mediated induction of CYP1A1 in MCF7-TETon-EGFR cells, a MCF7 variant in which EGFR expression can be controlled, was not affected by the activity status of EGFR or ERKs. Hence, EGFR signaling mutes both basal and ligand-induced expression of two aryl hydrocarbon receptor-responsive P450s in MCF10A cultures. However, these effects are cell context-dependent. Furthermore, CYP1A1 mRNA and protein abundance are not closely coupled in MCF10A cultures.

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Section: Egfr Inhibitor Modulation Of Egfr and Extracellularmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

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Epidermal Growth Factor Receptor Kinase Inhibitors Synergize with TCDD to Induce CYP1A1/1A2 in Human Breast Epithelial MCF10A Cells

Joiakim

Mathieu

Shelp

et al. 2016

Drug Metabolism and Disposition

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“…Several other human cell lines formed important models for AHR research appearing in DMD. In human mammary epithelial MCF10A cultures, p-anilinoaniline, an inhibitor of an E2 ubiquitin-conjugating enzyme implicated in AHR degradation, enhances TCDD-induced CYP1A1 transcription and AHR occupancy of the CYP1A1 promoter, with effects dependent on cell cycle phase (Elliott et al, 2012). In the same cell model, TCDD and inhibitors of epidermal growth factor receptor kinase induce CYP1A1 and 1A2 synergistically, and CYP1A1 mRNA and protein levels display notable discordance (Joiakim et al, 2016).…”

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confidence: 99%

Fifty Years of Aryl Hydrocarbon Receptor Research as Reflected in the Pages ofDrug Metabolism and Disposition

Riddick

2023

Drug Metab Dispos

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The induction of multiple drug-metabolizing enzymes by halogenated and polycyclic aromatic hydrocarbon toxicants is mediated by the aryl hydrocarbons receptor (AHR). This fascinating receptor also has natural dietary and endogenous ligands, and much is now appreciated about the AHR's developmental and physiological roles, as well as its importance in cancer and other diseases. The past several years has witnessed increasing emphasis on understanding the multifaceted roles of the AHR in the immune system. Most would agree that the "discovery" of the AHR occurred in 1976, with the report of specific binding of a high affinity radioligand in mouse liver, just three years after the launch of the journal Drug Metabolism and Disposition (DMD) in 1973. Over the ensuing fifty years, the AHR and DMD have led parallel and often intersecting lives. The overall goal of this minireview is to provide a decade-by-decade overview of major historical landmark discoveries in the AHR field and to highlight the numerous contributions made by publications appearing in the pages of DMD. It is hoped that this historical tour might inspire current and future research in the AHR field. Significance Statement With the launch of Drug Metabolism and Disposition (DMD) in 1973 and the discovery of the aryl hydrocarbon receptor (AHR) in 1976, the journal and the receptor have led parallel and often intersecting lives over the past fifty years. Tracing the history of the AHR can reveal how knowledge in the field has evolved to the present and highlight the important contributions made by discoveries reported in DMD. This may inspire additional DMD papers reporting future AHR landmark discoveries.

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p-Anilinoaniline Enhancement of Dioxin-Induced CYP1A1 Transcription and Aryl Hydrocarbon Receptor Occupancy of CYP1A1 Promoter: Role of the Cell Cycle

Cited by 2 publications

References 45 publications

Epidermal Growth Factor Receptor Kinase Inhibitors Synergize with TCDD to Induce CYP1A1/1A2 in Human Breast Epithelial MCF10A Cells

Epidermal Growth Factor Receptor Kinase Inhibitors Synergize with TCDD to Induce CYP1A1/1A2 in Human Breast Epithelial MCF10A Cells

Fifty Years of Aryl Hydrocarbon Receptor Research as Reflected in the Pages ofDrug Metabolism and Disposition

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