Arl-Hydrocarbon Receptor Based Antiestrogenicity of Diindolylmethane Analogs
Abstract
Research in our laboratory has been focused on the mechanism of inhibitory aryl hydrocarbon (Ah) receptor-estrogen receptor a (ER alpha) crosstalk in breast cancer cells, and results indicate that Ah receptor agonists inhibit estrogen (E2)-induced gene expression and cell proliferation (1,2). Moreover, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a high affinity ligand for the Ah receptor, inhibits age-dependent and carcinogen-induced mammary tumor formation and growth in female Sprague-Dawley rats, and a recent study reported that women accidentally exposed to TCDD in Seveso, Italy, over 20 years ago exhibit lower incidence rates of breast and endometrial cancer (3). Studies on various structural classes of AhR agonists have identified alternate substituted (1 ,3,6,8- or 2,4,6,8-) alkyl polychlorinated dibenzofurans (PCDFs) and substituted diindolylmethanes (DlMs) as selective Ah receptor modulators (SAhRMs) that are relative nontoxic but inhibit mammary tumor growth in rodent models (4). With financial support from this grant, I have been investigating the indirect antiestrogenic activity of substituted DIMs and applications of these compounds for treating mammary cancer (5-7).
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA409446
Entities
People
- Jeong E. Lee
Organizations
- Texas A&M University