The Breast Cancer Susceptibility Gene TOX3 Promotes Estrogen Synthesis: An RNA-sequencing and Network Study
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ABSTRACT:
PROVIDER: PRJNA677925 | ENA |
REPOSITORIES: ENA
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Project description:We aimed to explore the effect of the breast cancer susceptibility gene TOX3 on estrogen synthesis from the perspective of estrogen production, in an attempt to link abnormalities in hormone production with the development of breast cancer. After overexpression of TOX3, several crucial key genes and pathways that contribute to estrogen production were upregulated. Forced expression of TOX3 also promotes proliferation and inhibits apoptosis of granulosa cells. These findings discuss the possible impact of susceptibility genes and steroid hormones on breast cancer from the perspective of extra-mammary tissues such as those in the ovary, thus providing new insights for early prevention and treatment of breast cancer.
2021-02-04 | GSE161341 | GEO
Project description:Estrogen receptor α (ERα) is a key regulator of breast growth and breast cancer development. However, the role of ERα in metabolic reprogramming, a hallmark of cancer, is not well documented. In this study, using an integrated approach combining genome-wide mapping of chromatin bound ERα with estrogen induced transcript and metabolic profiling, we demonstrate that ERα reprograms metabolism upon estrogen stimulation, including changes in aerobic glycolysis, nucleotide and amino acid synthesis, and choline metabolism. We show, for the first time, that the ERα target gene choline phosphotransferase 1 (CHPT1) plays an essential role in estrogen induced increases in phosphatidylcholine (PtdCho) levels and that CHPT1 promotes tumorigenesis and proliferation. Furthermore, we show that CHPT1 is overexpressed in tumors compared to normal breast. We also demonstrate that ERα promotes aerobic glycolysis through increased expression of glycolytic genes. In conclusion, this study highlights the importance of ERα for metabolic alterations in breast cancer cells. Furthermore, overexpression of the ERα target CHPT1 in breast cancer supports its potential as a therapeutic target.
2016-10-12 | GSE74033 | GEO
Project description:Estrogen receptor α (ERα) is a key regulator of breast growth and breast cancer development. However, the role of ERα in metabolic reprogramming, a hallmark of cancer, is not well documented. In this study, using an integrated approach combining genome-wide mapping of chromatin bound ERα with estrogen induced transcript and metabolic profiling, we demonstrate that ERα reprograms metabolism upon estrogen stimulation, including changes in aerobic glycolysis, nucleotide and amino acid synthesis, and choline metabolism. We show, for the first time, that the ERα target gene choline phosphotransferase 1 (CHPT1) plays an essential role in estrogen induced increases in phosphatidylcholine (PtdCho) levels and that CHPT1 promotes tumorigenesis and proliferation. Furthermore, we show that CHPT1 is overexpressed in tumors compared to normal breast. We also demonstrate that ERα promotes aerobic glycolysis through increased expression of glycolytic genes. In conclusion, this study highlights the importance of ERα for metabolic alterations in breast cancer cells. Furthermore, overexpression of the ERα target CHPT1 in breast cancer supports its potential as a therapeutic target.
2016-10-12 | GSE74032 | GEO
Project description:Understanding how differentiation, microenvironment, and hormonal milieu influence human breast cell susceptibility to malignant transformation will require the use of physiologically relevant in vitro systems. We developed a 3D culture model that enables the propagation of normal estrogen receptor alpha (ER)+ cells. The purpose of this experiment was to assess ER functionality and compare estrogen-induced transcripts among samples and systems.
2018-06-15 | GSE115112 | GEO
Project description:We conducted RNA-seq from the Ginkgo leaves after UV-B treatment,and constructed the molecular regulatory network of flavonoids synthesis under UV-B radiation in G. biloba.
2019-12-13 | GSE141890 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE12248: Genetic architecture of murine skin inflammation and tumor susceptibility GSE21247: Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (carcinomas) GSE21263: Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (papillomas) GSE26273: Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (aCGH) Refer to individual Series
2010-12-22 | E-GEOD-21264 | biostudies-arrayexpress
Project description:Estrogen receptor-mediated proliferation of breast cancer cells is facilitated through expression of multiple primary target genes, products of which induce the secondary response to stimulation. To differentiate between the primary and secondary target genes of estrogen receptor signaling, we measured dynamics of protein expression induced by estradiol in MCF-7 breast cancer cells. Measurement of the global proteomic effects of estradiol by SILAC resulted in identification of 104 estradiol-regulated proteins, with only 41 corresponding genes having estrogen response elements (EREs). Selected reaction monitoring assays were used to validate 32 proteins and measure the dynamics of their expression within 72 hours upon estradiol stimulation and in the presence of 4-hydroxytamoxifen, thus confirming estrogen receptor-mediated signaling. Dynamics of protein expression revealed immediate early response proteins including TFF1 and CDK1 and delayed response proteins including CDK2 and NAB2. Presence or absence of EREs in the corresponding genes indicated early or delayed expression of proteins identified by SILAC. Finally, we measured accurate dynamics of estradiol-induced protein expression in the sub-network of primary and secondary targets of estrogen receptor. Interestingly, since NAB2 protein is also a repressor of EGR3-induced transcription, siRNA-mediated silencing of NAB2 resulted in the over-expression of some EGR3-induced proteins, such as ITGA2. To conclude, quantitative proteomics revealed secondary targets of estrogen receptor signaling potentially overlooked by genome-wide profiling of EREs and provided dynamics of protein expression in the network of transcription factors with a negative feedback loop.
2016-04-14 | PXD002797 | Pride
Project description:Mufudza2012 - Estrogen effect on the dynamics
of breast cancer
This deterministic model shows the
dynamics of breast cancer with immune response. The effects of
estrogen are incorporated to study its effects as a risk factor for
the disease.
This model is described in the article:
Assessing the effects of
estrogen on the dynamics of breast cancer.
Mufudza C, Sorofa W, Chiyaka
ET.
Comput Math Methods Med 2012; 2012:
473572
Abstract:
Worldwide, breast cancer has become the second most common
cancer in women. The disease has currently been named the most
deadly cancer in women but little is known on what causes the
disease. We present the effects of estrogen as a risk factor on
the dynamics of breast cancer. We develop a deterministic
mathematical model showing general dynamics of breast cancer
with immune response. This is a four-population model that
includes tumor cells, host cells, immune cells, and estrogen.
The effects of estrogen are then incorporated in the model. The
results show that the presence of extra estrogen increases the
risk of developing breast cancer.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000642.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-07-26 | BIOMD0000000642 | BioModels
Project description:We are using the ACI rat model of 17beta-estradiol induced mammary cancer to define the mechanisms through which estrogens contribute to breast cancer development; identify and functionally characterize the genetic variants that determine susceptibility; and define the hormone-gene-environment interactions that influence development of mammary cancer in this physiologically relevant rat model. Female ACI rats are uniquely susceptible to development of mammary cancer when treated continuously with physiologic levels of 17beta-estradiol. Induction of mammary cancer in female ACI rats occurs through a mechanism that is largely dependent upon estrogen receptor-alpha. Interval mapping analyses of progeny generated in intercrosses between susceptible ACI rats and resistant Brown Norway (BN) rats revealed seven quantitative trait loci (QTL), designated Emca3 (Estrogen-induced mammary cancer) through Emca9, each of which harbors one or more genetic determinants of mammary cancer susceptibility. Genes that reside within Emca8 on RNO5 and were differentially expressed between 17beta-estradiol treated ACI and ACI.BN-Emca8 congenic rats were identified as Emca8 candidates.
2013-02-08 | GSE39788 | GEO
Project description: Not available
| S-EPMC7945945 | biostudies-literature