Differences in 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible CYP1A1 expression in human breast carcinoma cell lines involve altered trans-acting factors.
Differences in expression of the CYP1A1 gene have previously been observed in human breast carcinoma cell lines exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Using an expression vector containing the functional 5'-regulatory region of human CYP1A1 (up to -1140) fused to the reporter gene CAT (for chloramphenicol acetyltransferase), the breast carcinoma cell lines, MCF-7, T47-D and ZR-75-1, classified as highly responsive to TCDD, were highly responsive to TCDD in the chloramphenicol acetyltransferase assay as well. Gel mobility shift assays have shown that these cell lines express a nuclear protein that binds the aryl hydrocarbon (Ah) receptor responsive element. The low or non-responsive cell lines, AL-1, BT-20 and CAMA-1, were low or non-responsive to TCDD in the chloramphenicol acetyltransferase assay, suggesting that the low-responsive phenotype is caused by altered trans-acting factors. However, the mechanism appears to differ among the cell lines. Whereas no induction was observed in AL-1, a fivefold induction in activity was observed in BT-20 and CAMA-1. The TCDD concentration giving half-maximum induction differed greatly between CAMA-1 and BT-20. The gel mobility shift assay showed the presence of a protein that bound specifically to the Ah responsive element in the non-responsive cell line AL-1, as well as the low-responsive cell lines, BT-20 and CAMA-1. The high basal activity but low induction observed in CAMA-1 may be due to an Ah receptor constitutively bound to the Ah responsive element.
Thomsen
J S
JS
Laboratory of Environmental Carcinogenesis, Fibiger Institute, Danish Cancer Society, Copenhagen.
Nissen
L
L
Stacey
S N
SN
Hines
R N
RN
Autrup
H
H
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D015534:Trans-Activators / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000072317:Polychlorinated Dibenzodioxins; D015534:Trans-Activators; D001189:Aryl Hydrocarbon Hydroxylases; D015500:Chloramphenicol O-Acetyltransferase