Archive | Genomics of Estrogen Receptor Signaling

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Estrogen receptor-α and aryl hydrocarbon receptor involvement in the actions of botanical estrogens in target cells.

Botanical estrogen (BE) dietary supplements are consumed by women as substitutes for loss of endogenous estrogens at menopause. To examine the roles of estrogen receptor α (ERα) and aryl hydrocarbon receptor (AhR) and their crosstalk in the actions of BEs, we studied gene regulation and proliferation responses to four widely used BEs, genistein, daidzein, and […]

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ERα-XPO1 crosstalk controls tamoxifen sensitivity in tumors by altering ERK5 cellular localization

Most breast cancer deaths occur in women with recurrent, ERα (+), metastatic tumors. There is a critical need for therapeutic approaches that include novel, targetable mechanism-based strategies by which ERα (+) tumors can be resensitized to endocrine therapies. The objective of this study was to validate a group of nuclear transport genes as potential biomarkers […]

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Design of pathway preferential estrogens that provide beneficial metabolic and vascular effects without stimulating reproductive tissues

There is great medical need for estrogens with favorable pharmacological profiles that support desirable activities for menopausal women, such as metabolic and vascular protection, but that lack stimulatory activities on the breast and uterus. We report the development of structurally novel estrogens that preferentially activate a subset of estrogen receptor (ER) signaling pathways and result […]

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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

With the advent of the -omics approaches our understanding of the chronic diseases like cancer and metabolic syndrome has improved. However, effective mining of the information in the large-scale datasets that are obtained from gene expression microarrays, deep sequencing experiments or metabolic profiling is essential to uncover and then effectively target the critical regulators of […]

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Differential Utilization of Nuclear and Extranuclear Receptor Signaling Pathways in the Actions of Estrogens, SERMs, and a Tissue-Selective Estrogen Complex (TSEC)

Estrogens act through nuclear and extranuclear initiated pathways involving estrogen receptors (ERs) to regulate gene expression and activate protein kinases. We investigated the involvement of extracellular signal-regulated kinase2 (ERK2) and ERα in the activities of estradiol (E2), conjugated estrogens (CEs), selective estrogen receptor modulators (SERMs), and a Tissue-Selective Estrogen Complex (TSEC), a combination of a […]

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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

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 […]

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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.

The forkhead transcription factor FOXM1 coordinates expression of cell cycle-related genes and plays a pivotal role in tumorigenesis and cancer progression. We previously showed that FOXM1 acts downstream of 14-3-3¿ signaling, the elevation of which correlates with a more aggressive tumor phenotype. However, the role that FOXM1 might play in engendering resistance to endocrine treatments […]

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Novel Roles for ERK5 and Cofilin as Critical Mediators Linking ERalpha-Driven Transcription, Actin Reorganization and Invasiveness in Breast Cancer.Madak-Erdogan Z., Ventrella R, Petry L., Katzenellenbogen BS , Molecular Cancer Research, 2014 May;12(5):714-27,

Cancer cell motility and invasiveness are fundamental characteristics of the malignant phenotype and are regulated through diverse signaling networks involving kinases and transcription factors. This study establishes an estrogen receptor (ERα)/MAPK (ERK5)/cofilin (CFL1) network that specifies the degree of breast cancer cell aggressiveness through coupling of actin reorganization and hormone receptor–mediated transcription. Using dominant negative […]

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Mechanism Enforcing the Estrogen Receptor Beta-Selectivity of Botanical Estrogens, Jiang, Y., Gong, P., Madak-Erdogan, Z., Martin, T., Jeyakumar, M., Carlson, K., Khan, I., Smillie, T.J., Chittiboyina, A.G., Rotte S.C.K., Helferich, W.G., Katzenellenbogen, J.A., Katzenellenbogen, B.S., FASEB Journal 2013 Nov;27(11):4406-18,

Because little is known about the actions of botanical estrogens (BEs), widely consumed by menopausal women, we investigated the mechanistic and cellular activities of some major BEs. We examined the interactions of genistein, daidzein, equol, and liquiritigenin with estrogen receptors ERα and ERβ, with key coregulators (SRC3 and RIP140) and chromatin binding sites, and the […]

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Integrative Genomics of Gene and Metabolic Regulation by Estrogen Receptors α and β and Coregulators, Madak-Erdogan Z, Charn T.H, Jiang Y, Liu E.T., Katzenellenbogen J.A., Katzenellenbogen B.S.Molecular Systems Biology 2013 Jun 18;9:676,

The closely related transcription factors (TFs), estrogen receptors ERα and ERβ, regulate divergent gene expression programs and proliferative outcomes in breast cancer. Utilizing breast cancer cells with ERα, ERβ, or both receptors as a model system to define the basis for differing response specification by related TFs, we show that these TFs and their key […]

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