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Title: Estrogen induced concentration dependent differential gene expression in human breast cancer (MCF7) cells: Role of transcription factors

Abstract

Highlights: •Estradiol (E2) at low dose induced cell proliferation in breast cancer cells. •E2 at high concentration induced cell stress in breast cancer cells. •Estrogen receptor physically interacts only with a few transcription factors. •Differential expression of genes with Oct-1 binding sites increased under stress. •Transcription factor binding sites showed distinct spatial distribution on genes. -- Abstract: Background: Breast cancer cells respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. The mechanism of this concentration dependent differential outcome is not well understood yet. Methodology: Meta-analysis of the expression data of MCF7 cells treated with low (1 nM) or high (100 nM) dose of estradiol (E2) was performed. We identified genes differentially expressed at the low or the high dose, and examined the nature of regulatory elements in the vicinity of these genes. Specifically, we looked for the difference in the presence, abundance and spatial distribution of binding sites for estrogen receptor (ER) and selected transcription factors (TFs) in the genomic region up to 25 kb upstream and downstream from the transcription start site (TSS) of these genes. Results: It was observed that at high dose E2 induced the expression of stress responsive genes, while at lowmore » dose, genes involved in cell cycle were induced. We found that the occurrence of transcription factor binding regions (TFBRs) for certain factors such as Sp1 and SREBP1 were higher on regulatory regions of genes expressed at low dose. At high concentration of E2, genes with a higher frequency of Oct-1 binding regions were predominantly involved. In addition, there were differences in the spatial distribution pattern of the TFBRs in the genomic regions among the two sets of genes. Discussion: E2 induced predominantly proliferative/metabolic response at low concentrations; but at high concentration, stress–rescue responses were induced. At high E2 concentration, classical genomic pathway involving ER binding to the regulatory regions was reduced, and alternate or indirect activation of genes through Oct-1 became more prominent.« less

Authors:
 [1];  [2]; ;  [1]
  1. Department of Biotechnology, PSG College of Technology, Coimbatore 641004 (India)
  2. Max Planck Institute for Biology of Ageing, Cologne (Germany)
Publication Date:
OSTI Identifier:
22239691
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 437; Journal Issue: 3; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL CYCLE; CELL PROLIFERATION; CONCENTRATION RATIO; DOSES; ESTRADIOL; MAMMARY GLANDS; NEOPLASMS; SPATIAL DISTRIBUTION; TRANSCRIPTION; TRANSCRIPTION FACTORS

Citation Formats

Chandrasekharan, Sabarinath, Kandasamy, Krishna Kumar, Dayalan, Pavithra, and Ramamurthy, Viraragavan. Estrogen induced concentration dependent differential gene expression in human breast cancer (MCF7) cells: Role of transcription factors. United States: N. p., 2013. Web. doi:10.1016/J.BBRC.2013.06.108.
Chandrasekharan, Sabarinath, Kandasamy, Krishna Kumar, Dayalan, Pavithra, & Ramamurthy, Viraragavan. Estrogen induced concentration dependent differential gene expression in human breast cancer (MCF7) cells: Role of transcription factors. United States. https://doi.org/10.1016/J.BBRC.2013.06.108
Chandrasekharan, Sabarinath, Kandasamy, Krishna Kumar, Dayalan, Pavithra, and Ramamurthy, Viraragavan. 2013. "Estrogen induced concentration dependent differential gene expression in human breast cancer (MCF7) cells: Role of transcription factors". United States. https://doi.org/10.1016/J.BBRC.2013.06.108.
@article{osti_22239691,
title = {Estrogen induced concentration dependent differential gene expression in human breast cancer (MCF7) cells: Role of transcription factors},
author = {Chandrasekharan, Sabarinath and Kandasamy, Krishna Kumar and Dayalan, Pavithra and Ramamurthy, Viraragavan},
abstractNote = {Highlights: •Estradiol (E2) at low dose induced cell proliferation in breast cancer cells. •E2 at high concentration induced cell stress in breast cancer cells. •Estrogen receptor physically interacts only with a few transcription factors. •Differential expression of genes with Oct-1 binding sites increased under stress. •Transcription factor binding sites showed distinct spatial distribution on genes. -- Abstract: Background: Breast cancer cells respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. The mechanism of this concentration dependent differential outcome is not well understood yet. Methodology: Meta-analysis of the expression data of MCF7 cells treated with low (1 nM) or high (100 nM) dose of estradiol (E2) was performed. We identified genes differentially expressed at the low or the high dose, and examined the nature of regulatory elements in the vicinity of these genes. Specifically, we looked for the difference in the presence, abundance and spatial distribution of binding sites for estrogen receptor (ER) and selected transcription factors (TFs) in the genomic region up to 25 kb upstream and downstream from the transcription start site (TSS) of these genes. Results: It was observed that at high dose E2 induced the expression of stress responsive genes, while at low dose, genes involved in cell cycle were induced. We found that the occurrence of transcription factor binding regions (TFBRs) for certain factors such as Sp1 and SREBP1 were higher on regulatory regions of genes expressed at low dose. At high concentration of E2, genes with a higher frequency of Oct-1 binding regions were predominantly involved. In addition, there were differences in the spatial distribution pattern of the TFBRs in the genomic regions among the two sets of genes. Discussion: E2 induced predominantly proliferative/metabolic response at low concentrations; but at high concentration, stress–rescue responses were induced. At high E2 concentration, classical genomic pathway involving ER binding to the regulatory regions was reduced, and alternate or indirect activation of genes through Oct-1 became more prominent.},
doi = {10.1016/J.BBRC.2013.06.108},
url = {https://www.osti.gov/biblio/22239691}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 437,
place = {United States},
year = {Fri Aug 02 00:00:00 EDT 2013},
month = {Fri Aug 02 00:00:00 EDT 2013}
}