Differential regulation of mouse Ah receptor gene expression in cell lines of different tissue origins

被引:57
作者
FitzGerald, CT
FernandezSalguero, P
Gonzalez, FJ
Nebert, DW
Puga, A
机构
[1] UNIV CINCINNATI, MED CTR, DEPT ENVIRONM HLTH, CTR ENVIRONM GENET, CINCINNATI, OH 45267 USA
[2] UNIV CINCINNATI, MED CTR, DEV BIOL GRAD PROGRAM, CINCINNATI, OH 45267 USA
[3] NCI, MOL CARCINOGENESIS LAB, NATL INST HLTH, BETHESDA, MD 20892 USA
关键词
D O I
10.1006/abbi.1996.0378
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The dioxin-binding Ah receptor (AHR) is a ligand-activated transcription factor that regulates the expression of several drug-metabolizing enzymes and has been implicated in immunosuppression, teratogenesis, cell-specific hyperplasia, and certain types of malignancies and toxicities. In order to examine tissue-specific regulation of the mouse Ah receptor gene (Ahr), we studied chimeric deletion constructs, containing the Ahr 5' flanking region and the firefly luciferase reporter gene (Luc). Transient transfection assays were performed in five established mouse cell lines: Hepa-1c1c7 (derived from hepatoma), JB6-C1 41-5a (epidermis), MLE-12 (lung epithelium), F9 (embryonal carcinoma), and NIH/3T3 (fibroblasts). Treatment of the cell lines included: dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin), retinoic acid (RA), cyclic adenosine 3':5'-monophosphate (cAMP), or 12-O-tertrdecanoylphorbol 13-acetate (TPA). Expression levels another, this finding was also confirmed by measurements of AHR mRNA steady-state levels. In all cell lines except F9 cells, maximal constitutive expression was observed with constructs containing 78 bp of Ahr promoter sequences, which include several putative binding sites for the transcription factor Sp1. In contrast, in F9 cells, inclusion of sequences between -174 and -78 resulted in a fourfold stimulation of constitutive expression, suggesting that other transcription factors are important in Ahr gene expression in these cells. In MLE-12 and 41-5a cells, expression was significantly decreased by treatment with dioxin, RA, cAMP, or TPA. A similar inhibitory effect was observed in cAMP-treated MLE-12 and F9 cells; this result was confirmed by RT-PCR measurements of AHR mRNA steady-state levels. These results indicate that both up- and down-regulation of the Ahr gene occur and exhibit tissue- and cell-type specificity. (C) 1996 Academic Press, Inc.
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收藏
页码:170 / 178
页数:9
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