GSE98514
Expression profiling of four replicates of MCF-7 cells treated with 100nM TCDD
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that binds pollutants, therapeutic drugs and endogenous ligands.  The AHR is expressed in all breast cancer subtypes and it can switch the aggressiveness of breast cancer cells from low to high depending on the ligand that it binds.  Jagged 1 (JAG1) is a NOTCH receptor ligand that is overexpressed in basal-like breast cancer.  JAG1 promotes breast cancer progression in part by increasing the migratory and invasive activity of breast cancer cells (BCCs).  The regulation of JAG1 by AHR in MCF-7 and MDA-MB-231 BCCs by two AHR ligands (TCDD and ITE) was investigated in this report.  TCDD is the prototype AHR ligand, and ITE is a non-toxic endogenous AHR ligand with anti-cancer activity.  Ingenuity pathway analysis (IPA) revealed a significant association between TCDD-regulated genes (TRGs) and cell movement.  Short interfering RNA (siRNA)-directed knockdown of AHR confirmed TCDD-stimulated decreases in JAG1 required AHR expression.  TCDD-induced reductions in JAG1 were inhibited by the AHR antagonist CH-223191.  The endogenous non-toxic AHR ligand ITE also reduced JAG1 by activating AHR in BCCs.  MDA-MB-231 are basal-like BCCs that are highly migratory and invasive, and these cancer cell attributes were significantly inhibited by ITE.  We reduced JAG1 with targeting siRNA, and the outcome mirrored ITE, it suppressed TNBC cell migration and invasive activity.  Collectively, these findings are the first showing that ITE is a tumor-suppressing AHR ligand in TNBC cells in part because it reduces JAG1 expression Overall design: Expression profiling of four replicates of MCF-7 cells treated with 100nM TCDD were compared to expression profiles of four control replicates of MCF-7 cells treated with DMSO by RNA-Seq