Dataset Information

Methylmercury promotes breast cancer cell proliferation.

ABSTRACT:

Context

Metalloestrogens are small ionic metals that activate the estrogen receptor (ER). Studies have shown that when metalloestrogens bind to the ER, there is an increase in transcription and expression of estrogen-regulated genes, which induces proliferation of estrogen-dependent breast cancer. Methylmercury (MeHg), a metalloestrogen, is present in the environment and is toxic at moderate to high concentrations. However, at lower concentrations MeHg may promote the proliferation of ER-positive breast cancers and protect cells against pro-apoptotic signals.

Objective

To investigate the effects of MeHg treatment on breast cancer cells in vitro.

Materials and methods

MCF7 breast cancer cells were treated with concentrations of MeHg ranging from 1?nM to 100?mM. Hg analysis was used to quantify intracellular mercury concentrations. Cell proliferation and apoptosis were determined by cell counting and Annexin-V staining, respectively.

Results

We defined a protocol that maximizes cellular exposure to mercury. Treatment of human ER-positive breast cancer cells with 1?nM MeHg promoted proliferation, while treatment with a concentration of 100?nM induced apoptosis.

Discussion and conclusions

Clarifying the effects of MeHg on breast cancer will improve our understanding of how environmental toxins affect tumor progression and may lead to the development of future therapeutic strategies.

SUBMITTER: Gaudet HM

PROVIDER: S-EPMC5984200 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Methylmercury promotes breast cancer cell proliferation.

Gaudet Hilary M HM Christensen Emily E Conn Brandon B Morrow Sara S Cressey Lauren L Benoit Janina J

Toxicology reports 20180525

<h4>Context</h4>Metalloestrogens are small ionic metals that activate the estrogen receptor (ER). Studies have shown that when metalloestrogens bind to the ER, there is an increase in transcription and expression of estrogen-regulated genes, which induces proliferation of estrogen-dependent breast cancer. Methylmercury (MeHg), a metalloestrogen, is present in the environment and is toxic at moderate to high concentrations. However, at lower concentrations MeHg may promote the proliferation of ER ...[more]

PMID: 29868453

Similar Datasets

Project description:BackgroundHistone deacetylases (HDACs) engage in the regulation of various cellular processes by controlling global gene expression. The dysregulation of HDACs leads to carcinogenesis, making HDACs ideal targets for cancer therapy. However, the use of HDAC inhibitors (HDACi) as single agents has been shown to have limited success in treating solid tumors in clinical studies. This study aimed to identify a novel downstream effector of HDACs to provide a potential target for combination therapy.MethodsTranscriptome sequencing and bioinformatics analysis were performed to screen for genes responsive to HDACi in breast cancer cells. The effects of HDACi on cell viability were detected using the MTT assay. The mRNA and protein levels of genes were determined by quantitative reverse transcription-PCR (qRT-PCR) and Western blotting. Cell cycle distribution and apoptosis were analyzed by flow cytometry. The binding of CREB1 (cAMP-response element binding protein 1) to the promoter of the KDELR (The KDEL (Lys-Asp-Glu-Leu) receptor) gene was validated by the ChIP (chromatin immunoprecipitation assay). The association between KDELR2 and protein of centriole 5 (POC5) was detected by immunoprecipitation. A breast cancer-bearing mouse model was employed to analyze the effect of the HDAC3-KDELR2 axis on tumor growth.ResultsKDELR2 was identified as a novel target of HDAC3, and its aberrant expression indicated the poor prognosis of breast cancer patients. We found a strong correlation between the protein expression patterns of HADC3 and KDELR2 in tumor tissues from breast cancer patients. The results of the ChIP assay and qRT-PCR analysis validated that HDAC3 transactivated KDELR2 via CREB1. The HDAC3-KDELR2 axis accelerated the cell cycle progression of cancer cells by protecting the centrosomal protein POC5 from proteasomal degradation. Moreover, the HDAC3-KDELR2 axis promoted breast cancer cell proliferation and tumorigenesis in vitro and in vivo.ConclusionOur results uncovered a previously unappreciated function of KDELR2 in tumorigenesis, linking a critical Golgi-the endoplasmic reticulum traffic transport protein to HDAC-controlled cell cycle progression on the path of cancer development and thus revealing a potential therapeutical target for breast cancer.

Dataset Information

Methylmercury promotes breast cancer cell proliferation.

Context

Objective

Materials and methods

Results

Discussion and conclusions

Publications

Methylmercury promotes breast cancer cell proliferation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets