Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA344561 | ENA |
REPOSITORIES: ENA
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Project description:Our previous studies demonstrated that specific inhibition of the BIG3-PHB2 complex, which is indispensable for estrogen (E2)-signaling activation, using ERAP, a dominant-negative peptide inhibitor, leads to the suppression of E2-dependent breast cancer cell growth in vitro and in vivo. However, duration of its effect is very short for clinical use. Here, we developed the chemically modified ERAP using stapling methods (stERAP; stapled ERAP) to improve duration of their antitumor effects. Tumor bearing mice treated with every 4 and 7 days with stERAP (1 mg/kg body weight) treatment effectively prevented the BIG3-PHB2 interaction, thereby releasing PHB2 to directly bind to both nuclear- and cytoplasmic ERalpha. This event led to the complete suppression of the E2-signalling pathways and ERalpha-positive breast cancer cell growth both in vitro and in vivo, but did not suppress the growth of normal mammary epithelial cells. Our findings suggest that the chemically modified stERAP may be a promising anti-tumor drug to suppress the growth of luminal-type breast cancer in clinical use.
2017-06-09 | GSE87378 | GEO
Project description:Gene expression underlying estrogen receptor activation versus inhibition in breast cancer cells
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Project description:ERα17p is a synthetic peptide corresponding to the sequence P295LMIKRSKKNSLALSLT311 of the estrogen receptor alpha (ERα) and initially synthesized to mimic its calmodulin binding site. ERα17p was subsequently found to elicit estrogenic responses in E2-deprived ERα-positive breast cancer cells, increasing proliferation and E2-dependent gene transcription. Surprisingly, in E2-supplemented media, ERα17p induced apoptosis and modified the actin network, influencing thereby cell motility. Here, we report that ERα17p induces a massive early (3h) transcriptional activity in breast cancer cell line T47D.
2012-07-31 | GSE39720 | GEO
Project description:We and others have proposed that coactivator binding inhibitors, which block the interaction of estrogen receptor and steroid receptor coactivators, may represent a potential class of new breast cancer therapeutics. The development of coactivator binding inhibitors has been limited, however, because many of the current molecules which are active in in vitro and biochemical assays are not active in cell-based assays. Our goal in this work was to prepare a coactivator binding inhibitor active in cellular models of breast cancer. To accomplish this, we used molecular dynamics simulations to convert a high-affinity stapled peptide with poor cell permeability into R4K1, a cell-penetrating stapled peptide. R4K1 displays high binding affinity for estrogen receptor ɑ, inhibits the formation of estrogen receptor/coactivator complexes, and distributes throughout the cell with a high percentage of nuclear localization. R4K1 represses native gene transcription mediated by estrogen receptor ɑ and inhibits proliferation of estradiol-stimulated MCF-7 cells. Using RNA-Seq, we demonstrate that almost all of the effects of R4K1 on global gene transcription are estrogen receptor-associated. This chemical probe provides a significant proof-of-concept for preparing cell-permeable stapled peptide inhibitors of the estrogen receptor/coactivator interaction.
2018-01-09 | GSE108308 | GEO
Project description:ERα17p is a synthetic peptide corresponding to the sequence P295LMIKRSKKNSLALSLT311 of the estrogen receptor alpha (ERα) and initially synthesized to mimic its calmodulin binding site. ERα17p was subsequently found to elicit estrogenic responses in E2-deprived ERα-positive breast cancer cells, increasing proliferation and E2-dependent gene transcription. Surprisingly, in E2-supplemented media, ERα17p induced apoptosis and modified the actin network, influencing thereby cell motility. Here, we report that ERα17p induces a massive early (3h) transcriptional activity in breast cancer cell line MDA-MB-231.
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2012-08-05 | E-GEOD-36586 | biostudies-arrayexpress
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:
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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.
2024-09-02 | BIOMD0000000642 | BioModels
Project description:Uncoupling effects of ERalfa on LKB1/AMPK interaction upon adiponectin exposure in breast cancer
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