title: G protein-coupled receptor 30 ligand G-1 increases aryl hydrocarbon receptor signalling by inhibition of tubulin assembly and cell cycle arrest in human MCF-7 cells.
abstract: Regulatory crosstalk between the aryl hydrocarbon receptor (AHR) and oestrogen receptor α (ERα) is well established. Apart from the nuclear receptors ERα and ERβ, oestrogen signalling further involves an unrelated G protein-coupled receptor termed GPR30. In order to investigate potential regulatory crosstalk, this study investigated the influence of G-1 as one of the few GPR30-specific ligands on the AHR regulon in MCF-7 cells. As a well-characterised model system, these human mammary carcinoma cells co-express all three receptors (AHR, ERα and GPR30) and are thus ideally suited to study corresponding regulatory pathway interactions on transcript level. Indeed, treatment with micromolar concentrations of the GPR30-specific agonist G-1 resulted in up-regulation of AHR as well as the transcripts for cytochromes P450 1A1 and 1B1, two well-known targets of the AHR regulon. While this was partly attributable to G-1-mediated inhibition of tubulin assembly and subsequent cell cycle arrest in the G2/M phase, the effects nevertheless required functional AHR. However, G-1-induced up-regulation of CYP 1A1 was not mediated by GPR30, as G15 antagonist treatment as well as a knockdown of GPR30 and AHR failed to inhibit this effect.
authors.affiliation: Department of Chemicals and Product Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, 10598, Berlin, Germany. Patrick.Tarnow@bfr.bund.de.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tarnow
authors.affiliation: Department of Chemicals and Product Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, 10598, Berlin, Germany.
authors.forename: Tewes
authors.initials: T
authors.lastname: Tralau
authors.affiliation: Department of Chemicals and Product Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, 10598, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Luch
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D003517:Cyclopentanes / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D011804:Quinolines / Q000494:pharmacology*; D020239:Receptor Cross-Talk; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000235:genetics; D015398:Signal Transduction; D013552:Swine; D014158:Transcription, Genetic; D014404:Tubulin / Q000378:metabolism*
chemical_list: C517943:1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone; D003517:Cyclopentanes; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C109584:GPER1 protein, human; D008024:Ligands; D011804:Quinolines; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D014404:Tubulin
keywords: AHR; Aryl hydrocarbon receptor; Cell cycle arrest; ER; G-1; GPER1; GPR30; Oestrogen receptor; Oestrogen signalling