Transcriptional control of local estrogen formation by aromatase in the breast

To, Sarah Quynh Giao; Knower, Kevin Christopher; Cheung, Vanessa; Simpson, Evan R.; Clyne, Colin

doi:10.1016/j.jsbmb.2014.05.004

Cited by 41 publications

(28 citation statements)

References 119 publications

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“…The perturbation of this estrobolome has been shown to influence both local and systemic levels of estrogen and its metabolites [13,94]. Malignant tissue in ER+ BC contains higher levels of estrogen metabolites as compared to normal breast tissue, attributed in part to altered intracrine signaling [95]. β-Glucuronidase prevalence was also found in nipple aspirate fluid of breast cancer survivors [65].…”

Section: Functional Pathwaysmentioning

confidence: 99%

Breast Cancer and Its Relationship with the Microbiota

Fernández

Reina-Pérez

Astorga

et al. 2018

IJERPH

264

197

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The microorganisms that live symbiotically in human beings are increasingly recognized as important players in health and disease. The largest collection of these microorganisms is found in the gastrointestinal tract. Microbial composition reflects both genetic and lifestyle variables of the host. This microbiota is in a dynamic balance with the host, exerting local and distant effects. Microbial perturbation (dysbiosis) could contribute to the risk of developing health problems. Various bacterial genes capable of producing estrogen-metabolizing enzymes have been identified. Accordingly, gut microbiota is capable of modulating estrogen serum levels. Conversely, estrogen-like compounds may promote the proliferation of certain species of bacteria. Therefore, a crosstalk between microbiota and both endogenous hormones and estrogen-like compounds might synergize to provide protection from disease but also to increase the risk of developing hormone-related diseases. Recent research suggests that the microbiota of women with breast cancer differs from that of healthy women, indicating that certain bacteria may be associated with cancer development and with different responses to therapy. In this review, we discuss recent knowledge about the microbiome and breast cancer, identifying specific characteristics of the human microbiome that may serve to develop novel approaches for risk assessment, prevention and treatment for this disease.

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Section: Functional Pathwaysmentioning

confidence: 99%

Breast Cancer and Its Relationship with the Microbiota

Fernández

Reina-Pérez

Astorga

et al. 2018

IJERPH

264

197

View full text Add to dashboard Cite

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“…We believe this is a conceptually important example of a new mechanism for promoting ER-positive breast cancer. Most of breast cancer cells are known to express higher levels of aromatase than non-cancerous cells [17]. Therefore, drugs like cortodoxone could be preferentially converted to estrogen in breast cancer cells, promoting the proliferation of cancerous cells.…”

Section: Discussionmentioning

confidence: 99%

AroER tri-screen™ is a novel functional assay to estimate both estrogenic and estrogen precursor activity of chemicals or biological specimens

Kanaya

Nguyen

et al. 2015

Breast Cancer Res Treat

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The purpose of the study is to define AroER tri-screen's utility for identifying endocrine-disrupting chemicals (EDCs) that target aromatase and/or estrogen receptor (ER), and to measure the total estrogenic activity in biological specimens. ER-positive, aromatase-expressing MCF-7 breast cancer cells were stably transfected with an estrogen responsive element (ERE)-driven luciferase reporter plasmid to yield a new high-throughput screening platform—the AroER tri-screen. AroER tri-screen was capable of identifying estrogen precursors, such as cortodoxone, which function as estrogens through a two-step conversion process in aromatase-expressing tissue. Furthermore, the system proved useful for assessing EDC activity in biologically relevant samples. Estimating these activities is critical because natural estrogens and estrogenic EDCs are important factors in ER-positive breast cancer risk. As our research demonstrates, incorporating functionally active aromatase into the AroER tri-screen produces a powerful and unique tool to (1) identify new EDCs targeting aromatase and/or ER; (2) discover novel EDCs activated by aromatase; and (3) estimate overall estrogenic activities in biological samples as a potential intermediate risk factor for breast cancer.

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“…4 and PII CYP19A1 promoter were previously described. 22,23 ZEB1 (Zinc finger E-box binding homeobox 1), EP300, E2F1 (E2F transcription factor 1) and RELA (RELA proto-oncogene, NF-κB subunit) plasmids were previously reported. [24][25][26][27] STAT3 (Signal transducer and activator of transcription 3), ER-β, ER-α and SF1 (Steroidogenic factor-1) plasmids were kindly provided by James Darnell (Rockefeller University, New York City, NY), Christopher K. Glass (University of California, United States), Rodolfo Rey (CEDIE, Argentina) and Ken-ichirou Morohashi (Kyushu University, Japan), respectively.…”

Section: Cell Lines and Its Stable Derivativesmentioning

confidence: 99%

CTBP1/CYP19A1/estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome

Massillo

Dalton

Porretti

et al. 2018

Intl Journal of Cancer

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Metabolic syndrome (MeS) increases prostate cancer (PCa) risk and aggressiveness. C-terminal binding protein 1 (CTBP1) is a transcriptional co-repressor of tumor suppressor genes that is activated by low NAD /NADH ratio. Previously, our group established a MeS and PCa mice model that identified CTBP1 as a novel link associating both diseases. We found that CTBP1 controls the transcription of aromatase (CYP19A1), a key enzyme that converts androgens to estrogens. The aim of this work was to investigate the mechanism that explains CTBP1 as a link between MeS and PCa based on CYP19A1 and estrogen synthesis regulation using PCa cell lines, MeS/PCa mice and adipose co-culture systems. We found that CTBP1 and E1A binding protein p300 (EP300) bind to CYP19A1 promoter and downregulate its expression in PC3 cells. Estradiol, through estrogen receptor beta, released CTBP1 from CYP19A1 promoter triggering its transcription and modulating PCa cell proliferation. We generated NSG and C57BL/6J MeS mice by chronically feeding animals with high fat diet. In the NSG model, CTBP1 depleted PCa xenografts showed an increase in CYP19A1 expression with subsequent increment in intratumor estradiol concentrations. Additionally, in C57BL/6J mice, MeS induced hypertrophy, hyperplasia and inflammation of the white adipose tissue, which leads to a proinflammatory phenotype and increased serum estradiol concentration. Thus, MeS increased PCa growth and Ctbp1, Fabp4 and IL-6 expression levels. These results describe, for the first time, a novel CTBP1/CYP19A1/Estradiol axis that explains, in part, the mechanism for prostate tumor growth increase by MeS.

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Transcriptional control of local estrogen formation by aromatase in the breast

Cited by 41 publications

References 119 publications

Breast Cancer and Its Relationship with the Microbiota

Breast Cancer and Its Relationship with the Microbiota

AroER tri-screen™ is a novel functional assay to estimate both estrogenic and estrogen precursor activity of chemicals or biological specimens

CTBP1/CYP19A1/estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome

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