3,3′-Diindolylmethane (DIM), a major in vivo product of acid-catalyzed oligomerization of indole-3-carbinol (I3C), is a promising anticancer agent present in vegetables of the Brassica genus. We investigated the effects of DIM on estrogen-regulated events in human breast cancer cells and found that DIM was a promoter-specific activator of estrogen receptor (ER) function in the absence of 17 beta-estradiol (E-2). DIM weakly inhibited the E-2-induced proliferation of ER-containing MCF-7 cells and induced proliferation of these cells in the absence of steroid, by approximately 60% of the E-2 response. DIM had little effect on proliferation of ER-deficient MDA-MB-231 cells, suggesting that it is not generally toxic at these concentrations. Although DIM did not bind to the ER in this concentration range, as shown by a competitive ER binding assay, it activated the ER to a DNA-binding species. DIM increased the lever of transcripts for the endogenous pS2 gene and activated the estrogen-responsive pERE-vit-CAT and pS2-tk-CAT reporter plasmids in transiently transfected MCF-7 cells. In contrast, DIM failed to activate transcription of the simple E-2- and diethylstilbesterol-responsive reporter construct pATC2. The estrogen antagonist ICI 182780 (7 alpha-[9-[(4,4,5,5,5-pentafluoropentyl)sulfonyl-]nonyl]-estra-1,3,5(10)-triene-3,17 beta-diol) was effective against DIM-induced transcriptional activity of the pERE-vit-CAT reporter, which further supports the hypothesis that DIM is acting through the ER. We demonstrated that ligand-independent activation of the ER in MCF-1 cells could be produced following treatment with the D1 dopamine receptor agonist SKF-82958 [(+\/-)6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepinehydrobromide]. We also demonstrated that: the agonist effects of SKF-82958 and DIM, but not of E-2, could be blocked by co-treatment with the protein kinase A (PKA) inhibitor H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide). These results have uncovered a promoter-specific, ligand-independent activation of ER signaling for DIM that may require activation by PKA, and suggest that this major I3C product may be a selective activator of ER function.<\/p>\n","protected":false},"template":"","mots_cles":[],"class_list":["post-57495","resume","type-resume","status-publish","hentry"],"acf":{"adresse":"\"BJELDANES LF,UNIV CALIF BERKELEY,DIV NUTR SCI & TOXICOL;119 MORGAN HALL;BERKELEY,CA 94720 USA. lfb@nature.berkeley.edu \"","annee":"2000","mois":"7","numero":"60:2","page":"167-177","auteurs":[{"ID":57491,"post_author":"0","post_date":"2018-12-04 07:40:10","post_date_gmt":"2018-12-04 06:40:10","post_content":"","post_title":"Bjeldanes","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"bjeldanes","to_ping":"","pinged":"","post_modified":"2018-12-04 07:40:10","post_modified_gmt":"2018-12-04 06:40:10","post_content_filtered":"","post_parent":0,"guid":"https:\/\/aprifel-pp.mentalworks.biz\/fr\/auteur\/bjeldanes\/","menu_order":0,"post_type":"auteur_resume","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":57492,"post_author":"0","post_date":"2018-12-04 07:40:10","post_date_gmt":"2018-12-04 06:40:10","post_content":"","post_title":"Chang","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"chang-16","to_ping":"","pinged":"","post_modified":"2018-12-04 07:40:10","post_modified_gmt":"2018-12-04 06:40:10","post_content_filtered":"","post_parent":0,"guid":"https:\/\/aprifel-pp.mentalworks.biz\/fr\/auteur\/chang-16\/","menu_order":0,"post_type":"auteur_resume","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":57493,"post_author":"0","post_date":"2018-12-04 07:40:11","post_date_gmt":"2018-12-04 06:40:11","post_content":"","post_title":"Firestone","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"firestone","to_ping":"","pinged":"","post_modified":"2018-12-04 07:40:11","post_modified_gmt":"2018-12-04 06:40:11","post_content_filtered":"","post_parent":0,"guid":"https:\/\/aprifel-pp.mentalworks.biz\/fr\/auteur\/firestone\/","menu_order":0,"post_type":"auteur_resume","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":57494,"post_author":"0","post_date":"2018-12-04 07:40:12","post_date_gmt":"2018-12-04 06:40:12","post_content":"","post_title":"Riby","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"riby","to_ping":"","pinged":"","post_modified":"2018-12-04 07:40:12","post_modified_gmt":"2018-12-04 06:40:12","post_content_filtered":"","post_parent":0,"guid":"https:\/\/aprifel-pp.mentalworks.biz\/fr\/auteur\/riby\/","menu_order":0,"post_type":"auteur_resume","post_mime_type":"","comment_count":"0","filter":"raw"}],"sources":[{"ID":46946,"post_author":"0","post_date":"2018-12-04 04:09:33","post_date_gmt":"2018-12-04 03:09:33","post_content":"","post_title":"BIOCHEMICAL PHARMACOLOGY","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"biochemical-pharmacology","to_ping":"","pinged":"","post_modified":"2018-12-04 04:09:33","post_modified_gmt":"2018-12-04 03:09:33","post_content_filtered":"","post_parent":0,"guid":"https:\/\/aprifel-pp.mentalworks.biz\/fr\/source\/biochemical-pharmacology\/","menu_order":0,"post_type":"source","post_mime_type":"","comment_count":"0","filter":"raw"}]},"yoast_head":"\n