Transforming growth factor-beta1 coregulates mRNA expression of aryl hydrocarbon receptor and cell-cycle-regulating genes in human cancer cell lines.
Transforming growth factor (TGF)-beta1 down-regulates mRNA expression of the aryl hydrocarbon receptor (AhR) and of AhR-inducible genes in A549 cells. Here, we describe a dose-dependent inhibition of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced cytochrome P450 (CYP) 1A1, CYP1B1 and NADPH-quinone-oxidoreductase (NMO-1) mRNA expression as well as TCDD-induced 7-ethoxyresorufin-O-deethylase (EROD) activity in MDA-MB 231 cells. The AhR mRNA expression was not affected by TGF-beta1. TGF-beta-responsiveness was investigated by examining the effect on the expression of responsive genes. While TGF-beta1 up-regulates mRNA expression of TGF-beta1 and TIEG (TGF-beta-inducible early gene) as well as luciferase activity of a responsive reporter plasmid in both cell lines, a down-regulation of c-myc and cyclin A mRNA expression was only found in A549 cells. Furthermore, TGF-beta1 inhibits only cell proliferation of A549 but not of MDA-MB 231 cells. The results show a coregulation of mRNA expression of AhR and cell-cycle regulating genes, and further indicate that the AhR may be involved in regulation of cell proliferation.
Döhr
O
O
Department of Toxicology, Heinrich-Heine-University of Düsseldorf, Auf'm Hennekamp 50, Düsseldorf, 40225, Germany.
Abel
J
J
D001189:Aryl Hydrocarbon Hydroxylases; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D019925:Cyclin A / Q000096:biosynthesis*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis; D008175:Lung Neoplasms; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D019925:Cyclin A; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D003577:Cytochrome P-450 Enzyme System; D008156:Luciferases; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D016660:NAD(P)H Dehydrogenase (Quinone)