Interaction of PAH-related compounds with the alpha and beta isoforms of the estrogen receptor.
The ability of several 4- and 5-ring polycyclic aromatic hydrocarbons (PAHs), heterocyclic PAHs, and their monohydroxy derivatives to interact with the estrogen receptor (ER) alpha and beta isoforms was examined. Only compounds possessing a hydroxyl group were able to compete with 3H-labeled 17beta-estradiol (E2) for binding to either a glutathione-S-transferase and human ERalpha D, E, and F domain fusion protein (GST-hERalphadef) or to the full-length human ERbeta. Competitive binding was comparable for both isoforms, with IC(50) values ranging from 20 to 300 nM (E2 IC(50) approximately 3 nM). However, several compounds were able to induce reporter gene expression preferentially through mERbeta, using MCF-7 cells transiently transfected with either a Gal4-human ERalphadef or Gal4-mouse ERbetadef construct, as well as a Gal4-regulated reporter. These data extend the number and type of PAH-related compounds capable of interacting with ERalpha and ERbeta, and provides additional evidence that even though some compounds may possess a similar affinity for both ER isoforms, the capacity for transcriptional activation can still be isoform-specific.
Fertuck
K C
KC
Department of Biochemistry and Molecular Biology, National Food Safety and Toxicology Center, Michigan State University, Wilson Road, East Lansing, MI 48824-1319, USA.
Kumar
S
S
Sikka
H C
HC
Matthews
J B
JB
Zacharewski
T R
TR
D000818:Animals; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000235:genetics; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006576:Heterocyclic Compounds, 4 or More Rings / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D051379:Mice; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006576:Heterocyclic Compounds, 4 or More Rings; D011084:Polycyclic Aromatic Hydrocarbons; D011960:Receptors, Estrogen; D004958:Estradiol