TRANSFORMING GROWTH FACTOR-BETA(1) COREGULATES MESSENGER-RNA EXPRESSION OF ARYL-HYDROCARBON RECEPTOR AND CELL-CYCLE-REGULATING GENES IN HUMAN CANCER CELL-LINES

Transforming growth factor (TGF)-beta(1) down-regulates mRNA expressio n 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 wel l as TCDD-induced 7-ethoxyresorufin-O-deethylase (EROD) activity in MD A-MB 231 cells. The AhR mRNA expression was not affected by TGF-beta(1 ). TGF-beta-responsiveness was investigated by examining the effect on the expression of responsive genes, while TGF-beta(1) up-regulates mR NA expression of TGF-beta(1) and TIEG (TGF-beta-inducible early gene) as well as luciferase activity of a responsive reporter plasmid in bot h cell lines, a down-regulation of c-myc and cyclin A mRNA expression was only found in A549 cells. Furthermore, TGF-beta(1) inhibits only c ell proliferation of A549 but not of MDA-MB 231 cells. The results sho w a coregulation of mRNA expression of AhR and cell-cycle regulating g enes, and further indicate that the AhR may be involved in regulation of cell proliferation. (C) 1997 Academic Press.