title: High metabolization of catecholestrogens by type 1 estrogen sulfotransferase (hEST1).
abstract: Recently, two types of estrogen sulfotransferase, chronologically named types 1 and 2 estrogen sulfotransferase (hEST1 and hEST2), have been described. Since hEST2 selectively catalyzes the sulfonation of ethinyl estradiol as well as that of estrone (E1) and estradiol (E2), but poorly the sulfonation of catecholestrogens, we wanted to assess the ability of hEST1 to metabolize these compounds. We overexpressed hEST1 in Escherichia coli in fusion with GST, then purified the enzyme using a glutathione affinity column, and obtained GST-free enzyme by digestion with thrombin. Using [35S]-phosphosadenosine phosphosulfate (PAPS) as cofactor, we showed that hEST1 efficiently metabolizes the transformation of 2-OH-E2 and 2-OH-E1. However, the transformation of 4-OH-E1 and 4-OH-E2 is much less efficient. Our results also show that hEST1 metabolizes more efficiently E2 than E1. Since hEST1 mRNA is produced from the same gene as MPST using different alternative promoters and since it is expressed in most breast cancer cells (MCF-7, ZR-75-1, T47-D, MDA-231, and MDA-418), studies of the expression and activity of hEST1 will be most important to have a better knowledge about its involvement in the control of the genotoxicity of estrogens and catecholestrogens.
authors.affiliation: Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL), 2705 Laurier Boulevard, Que., Canada G1V 4G2.
authors.forename: F
authors.initials: F
authors.lastname: Faucher
authors.forename: L
authors.initials: L
authors.lastname: Lacoste
authors.forename: I
authors.initials: I
authors.lastname: Dufort
authors.forename: V
authors.initials: V
authors.lastname: Luu-The
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D002393:Estrogens, Catechol / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D002393:Estrogens, Catechol; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015238:Sulfotransferases; C020122:estrone sulfotransferase