The estrogen receptors (ERs) ERα and ERβ mediate the actions of endogenous estrogens as well as those of botanical estrogens (BEs) present in plants. BEs are ingested in the diet and also widely consumed by postmenopausal women as dietary supplements, often as a substitute for the loss of endogenous estrogens at menopause. However, their activities and efficacies, and similarities and differences in gene expression programs with respect to endogenous estrogens such as estradiol (E2) are not fully understood. Because gene expression patterns underlie and control the broad physiological effects of estrogens, we have investigated and compared the gene networks that are regulated by different BEs and by E2. Our aim was to determine if the soy and licorice BEs control similar or different gene expression programs and to compare their gene regulations with that of E2. Gene expression was examined by RNA-Seq in human breast cancer (MCF7) cells treated with control vehicle, BE or E2. These cells contained three different complements of ERs, ERα only, ERα+ERβ, or ERβ only, reflecting the different ratios of these two receptors in different human breast cancers and in different estrogen target cells. Using principal component, hierarchical clustering, and gene ontology and interactome analyses, we found that BEs regulated many of the same genes as did E2. The genes regulated by each BE, however, were somewhat different from one another, with some genes being regulated uniquely by each compound. The overlap with E2 in regulated genes was greatest for the soy isoflavones genistein and S-equol, while the greatest difference from E2 in gene expression pattern was observed for the licorice root BE liquiritigenin. The gene expression pattern of each ligand depended greatly on the cell background of ERs present. Despite similarities in gene expression pattern with E2, the BEs were generally less stimulatory of genes promoting proliferation and were more pro-apoptotic in their gene regulations than E2. The distinctive patterns of gene regulation by the individual BEs and E2 may underlie differences in the activities of these soy and licorice-derived BEs in estrogen target cells containing different levels of the two ERs. PMID:25363786
Transcriptomic analysis identifies gene networks regulated by estrogen receptor α (ERα) and ERβ that control distinct effects of different botanical estrogens. Gong P, Madak-Erdogan Z, Li J1, Cheng J1, Greenlief CM1, Helferich WG, Katzenellenbogen JA, Katzenellenbogen B. Nucl Recept Signal. 2014 Sep 12;12S
By firstname.lastname@example.org on November 8, 2014 in Botanical Estrogens, Breast Cancer, Genomics of Estrogen Receptor Signaling, Systems Biology
- Bazedoxifene and conjugated estrogen combination maintains metabolic homeostasis and benefits liver health
- Estrogens and female liver health
- Estrogen receptor-α and aryl hydrocarbon receptor involvement in the actions of botanical estrogens in target cells.
- ERα-XPO1 crosstalk controls tamoxifen sensitivity in tumors by altering ERK5 cellular localization
- Estrogen and Microbiota Crosstalk: Should We Pay Attention?
The forkhead transcription factor FOXM1 promotes endocrine resistance and invasiveness in estrogen receptor-positive breast cancer by expansion of stem-like cancer cells.Bergamaschi, A., Madak-Erdogan, Z., Kim Y., Choi Y.L., Lu H. and Katzenellenbogen, B.S. , Breast Cancer Res. 2014 Sep 12;16(5):436.