another reason to eat your broccoli/brussel sprouts!

[Lani]

1: Mol Endocrinol. 2006 Aug 10; [Epub ahead of print] Links
Indole-3-Carbinol (I3C) selectively uncouples expression and activity of estrogen receptor subtypes in human breast cancer cells.

Sundar SN,
Kerekatte V,
Equinozio CN,
Doan VB,
Bjeldanes LF,
Firestone GL.
Department of Molecular and Cell Biology and the Cancer Research Laboratory, and Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, CA 94720-3200.
Estrogen responsive breast cancer cells, such as MCF7 and T47D cells, express both estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta). Indole-3-carbinol (I3C) strongly down-regulated ERalpha protein and transcript levels, without altering the level of ERbeta protein, in both cell lines. In cells transfected with the ERalpha promoter linked to a luciferase gene reporter, I3C ablated ERalphapromoter activity. Propyl pyrazole triol (PPT) is a highly selective ERalphaagonist, whereas, 17beta-estradiol (E) activates both ERalpha and ERbeta. I3C treatment inhibited the PPT and E induced proliferation of breast cancer cells, disrupted the PPT and E stimulation of estrogen response element (ERE) driven reporter plasmid activity as well as of endogeneous progesterone receptor transcripts. Using an in vitro ERE binding assay, I3C was shown to inhibit the level of functional ERalpha, and stimulated the level of ERE binding ERbetaeven though the protein levels of this receptor remained constant. In ERalpha-/ERbeta+ MDA-MB-231 breast cancer cells, I3C treatment stimulated a six fold increase in binding of ERbeta to the ERE. I3C also induced ERE and AP-1 driven reporter plasmid activities in the absence of an estrogen receptor agonist suggesting that ERbeta is activated in indole treated cells. Taken together, our results demonstrate that the expression and function of ERalpha and ERbetacan be uncoupled by I3C with a key cellular consequence being a significantly higher ERbeta:ERalpha ratio that is generally highly associated with anti-proliferative status of human breast cancer cells.
PMID: 16901971 [PubMed - as supplied by publisher]