Gene expression profiling reveals that the regulation of estrogen-responsive element-independent genes by 17β-estradiol-estrogen receptor β is uncoupled from the induction of phenotypic changes in cell models

Li, Xiaodong; Nott, Stephanie L.; Huang, Yanfang; Hilf, Russell; Bambara, Robert A.; Qiu, Xing; Yakovlev, Andrei; Welle, Stephen; Muyan, Mesut

doi:10.1677/jme-07-0156

Cited by 9 publications

(73 citation statements)

References 81 publications

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“…Our recent studies aimed at dissecting nuclear estrogen signaling pathways suggest that genomic responses from the ERE-dependent signaling pathway to E2-ER are required to induce phenotypic changes (10,11). These findings raise the possibility that targeted regulation of ERE-driven genes could be a basis for the development of a therapy for ER-negative breast cancers.…”

Section: Designer Monotransregulators Provide a Basis For A Transcripmentioning

confidence: 99%

“…MDA-MB-231 cells were cultured as described (10,11). BT-549 cells obtained from ATCC (Manassas, VA, USA) were maintained in RPMI-164 supplemented with 10 μg/mL insulin (Sigma-Aldrich) and with 10% fetal bovine serum (FBS, Invitrogen).…”

Section: Cell Culture and Biochemical Assaysmentioning

confidence: 99%

“…BT-549 cells obtained from ATCC (Manassas, VA, USA) were maintained in RPMI-164 supplemented with 10 μg/mL insulin (Sigma-Aldrich) and with 10% fetal bovine serum (FBS, Invitrogen). Recombinant adenoviruses were generated and tittered as described (10,11).…”

Section: Cell Culture and Biochemical Assaysmentioning

confidence: 99%

“…The total RNA was subjected to quantitative PCR (qPCR) using custom TaqMan Low Density Arrays (Foster City, CA, USA) (10,11). Relative quantification analysis was performed using the comparative C T method (15).…”

Section: Endogenous Gene Expressionmentioning

confidence: 99%

“…MDA-MB-231 (5,000 cells) or BT-549 (10,000 cells) cells were plated in 24-well culture plates in phenol red-free medium containing 10% CD-FBS for 24 h. Cells were infected with or without 10 -9 M E2 for 6 d. At termination, cells were subjected to counting using a hemocytometer and a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (Invitrogen) (10,11).…”

Section: Cellular Proliferationmentioning

confidence: 99%

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Designer Monotransregulators Provide a Basis for a Transcriptional Therapy for De Novo Endocrine-Resistant Breast Cancer

Nott

Huang

Kalkanoglu

et al. 2009

Mol Med

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The main circulating estrogen hormone 17β-estradiol (E2) contributes to the initiation and progression of breast cancer. Estrogen receptors (ERs), as transcription factors, mediate the effects of E2. Ablation of the circulating E2 and/or prevention of ER functions constitute approaches for ER-positive breast cancer treatments. These modalities are, however, ineffective in de novo endocrine-resistant breast neoplasms that do not express ERs. The interaction of E2-ERs with specific DNA sequences, estrogen responsive elements (EREs), of genes constitutes one genomic pathway necessary for cellular alterations. We herein tested the prediction that specific regulation of ERE-driven genes by an engineered monomeric and constitutively active transcription factor, monotransregulator, provides a basis for the treatment of ER-negative breast cancer. Using adenovirus infected ER-negative MDA-MB-231 cells derived from a breast adenocarcinoma, we found that the monotransregulator, but not the ERE-binding defective counterpart, repressed cellular proliferation and motility, and induced apoptosis through expression of genes that required ERE interactions. Similarly, the monotransregulator suppressed the growth of ER-negative BT-549 cells derived from a breast-ductal carcinoma. Moreover, the ERE-binding monotransregulator repressed xenograft tumor growth in a nude mice model. Thus, specific regulation of genes bearing EREs could offer a therapeutic approach for de novo endocrine-resistant breast cancers.

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Section: Designer Monotransregulators Provide a Basis For A Transcripmentioning

confidence: 99%

Section: Cell Culture and Biochemical Assaysmentioning

confidence: 99%

Section: Cell Culture and Biochemical Assaysmentioning

confidence: 99%

Section: Endogenous Gene Expressionmentioning

confidence: 99%

Section: Cellular Proliferationmentioning

confidence: 99%

See 3 more Smart Citations

Designer Monotransregulators Provide a Basis for a Transcriptional Therapy for De Novo Endocrine-Resistant Breast Cancer

Nott

Huang

Kalkanoglu

et al. 2009

Mol Med

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Molecular mechanism of estrogen–estrogen receptor signaling

Yaşar

Ayaz

User

et al. 2016

Reprod Medicine & Biology

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345

240

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Abstract17β‐Estradiol (E2), as the main circulating estrogen hormone, regulates many tissue and organ functions in physiology. The effects of E2 on cells are mediated by the transcription factors and estrogen receptor (ER)α and ERβ that are encoded by distinct genes. Localized at the peri‐membrane, mitochondria, and the nucleus of cells that are dependent on estrogen target tissues, the ERs share similar, as well as distinct, regulatory potentials. Different intracellular localizations of the ERs result in dynamically integrated and finely tuned E2 signaling cascades that orchestrate cellular growth, differentiation, and death. The deregulation of E2–ER signaling plays a critical role in the initiation and progression of target tissue malignancies. A better understanding of the complex regulatory mechanisms that underlie ER actions in response to E2 therefore holds a critical trajectory for the development of novel prognostic and therapeutic approaches with substantial impacts on the systemic management of target tissue diseases.

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Modulation of neural gene networks by estradiol in old rhesus macaque females

Cervera-Juanes,

Zimmerman,

Wilhelm

et al. 2024

GeroScience

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The postmenopausal decrease in circulating estradiol (E2) levels has been shown to contribute to several adverse physiological and psychiatric effects. To elucidate the molecular effects of E2 on the brain, we examined differential gene expression and DNA methylation (DNAm) patterns in the nonhuman primate brain following ovariectomy (Ov) and subsequent subcutaneous bioidentical E2 chronic treatment. We identified several dysregulated molecular networks, including MAPK signaling and dopaminergic synapse response, that are associated with ovariectomy and shared across two different brain areas, the occipital cortex (OC) and prefrontal cortex (PFC). The finding that hypomethylation (p = 1.6 × 10−51) and upregulation (p = 3.8 × 10−3) of UBE2M across both brain regions provide strong evidence for molecular differences in the brain induced by E2 depletion. Additionally, differential expression (p = 1.9 × 10−4; interaction p = 3.5 × 10−2) of LTBR in the PFC provides further support for the role E2 plays in the brain, by demonstrating that the regulation of some genes that are altered by ovariectomy may also be modulated by Ov followed by hormone replacement therapy (HRT). These results present real opportunities to understand the specific biological mechanisms that are altered with depleted E2. Given E2’s potential role in cognitive decline and neuroinflammation, our findings could lead to the discovery of novel therapeutics to slow cognitive decline. Together, this work represents a major step toward understanding molecular changes in the brain that are caused by ovariectomy and how E2 treatment may revert or protect against the negative neuro-related consequences caused by a depletion in estrogen as women approach menopause.

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Gene expression profiling reveals that the regulation of estrogen-responsive element-independent genes by 17β-estradiol-estrogen receptor β is uncoupled from the induction of phenotypic changes in cell models

Cited by 9 publications

References 81 publications

Designer Monotransregulators Provide a Basis for a Transcriptional Therapy for De Novo Endocrine-Resistant Breast Cancer

Designer Monotransregulators Provide a Basis for a Transcriptional Therapy for De Novo Endocrine-Resistant Breast Cancer

Molecular mechanism of estrogen–estrogen receptor signaling

Modulation of neural gene networks by estradiol in old rhesus macaque females

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