Restoration of aryl hydrocarbon (Ah) responsiveness in MDA-MB-231 human breast cancer cells by transient expression of the estrogen receptor.
MDA-MB-231 human breast cancer cells express the aryl hydrocarbon (Ah) receptor; however, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) does not induce CYP1A1 gene expression or chloramphenicol acetyltransferase (CAT) activity in cells transiently transfected with pRNH11c, and Ah-responsive plasmid derived from the 5'-flanking region of the human CYP1A1 gene. However, when MDA-MB-231 cells were treated with 10 nM TCDD and co-transfected with pRHN11c and a human estrogen receptor (hER) expression plasmid (delta hER), there was approximately a 10-fold increase in CAT activity. The restoration of Ah-responsiveness in MDA-MB-231 cells by expression of nuclear hER was highly specific since parallel studies in which plasmids that express the progesterone receptor and Jun nuclear proteins did not restore Ah-responsiveness to this cell line. Moreover, in cells transiently transfected with the pRNH11c and delta hER plasmids and 10 nM TCDD, overexpression of the Jun protein inhibited the effects of the hER on Ah-responsiveness. Plasmids that express truncated forms of the hER were also active in MDA-MB-231 cells but were not as effective as the complete hER. These studies reveal a unique function for the ER in MDA-MB-231 cells in which expression of this protein results in restoration of Ah-responsiveness.
Thomsen
J S
JS
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843-4466.
Wang
X
X
Hines
R N
RN
Safe
S
S
D000230:Adenocarcinoma / Q000201:enzymology / Q000503:physiopathology* / Q000648:ultrastructure; D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology / Q000503:physiopathology* / Q000648:ultrastructure; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004790:Enzyme Induction; D006801:Humans; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; D015500:Chloramphenicol O-Acetyltransferase