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Depletion of CTCF in Breast Cancer Cells Selectively Induces Cancer Cell Death via p53
CCCTC-binding factor (CTCF), a ubiquitous 11-zinc finger multifunctional protein, has distinct molecular functions, such as transcriptional activation, repression, and chromatin barrier activity, in a locus-specific manner. Elevated CTCF levels in breast cancer cells are known to contribute to tumor...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ivyspring International Publisher
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559975/ https://www.ncbi.nlm.nih.gov/pubmed/28819414 http://dx.doi.org/10.7150/jca.18818 |
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author | Lee, Ji-Yeon Mustafa, Muhammad Kim, Clara Yuri Kim, Myoung Hee |
author_facet | Lee, Ji-Yeon Mustafa, Muhammad Kim, Clara Yuri Kim, Myoung Hee |
author_sort | Lee, Ji-Yeon |
collection | PubMed |
description | CCCTC-binding factor (CTCF), a ubiquitous 11-zinc finger multifunctional protein, has distinct molecular functions, such as transcriptional activation, repression, and chromatin barrier activity, in a locus-specific manner. Elevated CTCF levels in breast cancer cells are known to contribute to tumorigenesis; however, the underlying mechanism remains elusive. We investigated the effect of CTCF expression on breast cancer cell survival and elucidated its mechanism. CTCF depletion in MCF-7 cells led to a decreased cell growth and proliferation, surpassing the growth of normal cells under co-culture system of MCF-7-GFP and MCF10A. Here we propose that the phenotypes observed in CTCF-depleted MCF-7 cancer cells, such as reduced cell proliferation, increased apoptosis, and cell cycle arrest, are closely linked with the activation of p53. The consensus CTCF-binding site, located approximately 800 bp upstream of the first exon of TP53, was marked by H3K27me3, but not by the active mark H3K4me3, although CTCF is expressed. Knockdown of CTCF conversely led to the recruitment of H3K4me3 instead of H3K27me3, accompanying with the higher enrichment of PolII in the proximal promoter region of TP53. With the activation of p53, increased p21 and Bax expressions were observed in CTCF knockdown MCF-7 cells. Elucidating functional roles of CTCF and regulation mechanisms may help to guide CTCF and/or its related molecules as a therapeutic target to prevent cancer cell growth. |
format | Online Article Text |
id | pubmed-5559975 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-55599752017-08-17 Depletion of CTCF in Breast Cancer Cells Selectively Induces Cancer Cell Death via p53 Lee, Ji-Yeon Mustafa, Muhammad Kim, Clara Yuri Kim, Myoung Hee J Cancer Research Paper CCCTC-binding factor (CTCF), a ubiquitous 11-zinc finger multifunctional protein, has distinct molecular functions, such as transcriptional activation, repression, and chromatin barrier activity, in a locus-specific manner. Elevated CTCF levels in breast cancer cells are known to contribute to tumorigenesis; however, the underlying mechanism remains elusive. We investigated the effect of CTCF expression on breast cancer cell survival and elucidated its mechanism. CTCF depletion in MCF-7 cells led to a decreased cell growth and proliferation, surpassing the growth of normal cells under co-culture system of MCF-7-GFP and MCF10A. Here we propose that the phenotypes observed in CTCF-depleted MCF-7 cancer cells, such as reduced cell proliferation, increased apoptosis, and cell cycle arrest, are closely linked with the activation of p53. The consensus CTCF-binding site, located approximately 800 bp upstream of the first exon of TP53, was marked by H3K27me3, but not by the active mark H3K4me3, although CTCF is expressed. Knockdown of CTCF conversely led to the recruitment of H3K4me3 instead of H3K27me3, accompanying with the higher enrichment of PolII in the proximal promoter region of TP53. With the activation of p53, increased p21 and Bax expressions were observed in CTCF knockdown MCF-7 cells. Elucidating functional roles of CTCF and regulation mechanisms may help to guide CTCF and/or its related molecules as a therapeutic target to prevent cancer cell growth. Ivyspring International Publisher 2017-07-05 /pmc/articles/PMC5559975/ /pubmed/28819414 http://dx.doi.org/10.7150/jca.18818 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Lee, Ji-Yeon Mustafa, Muhammad Kim, Clara Yuri Kim, Myoung Hee Depletion of CTCF in Breast Cancer Cells Selectively Induces Cancer Cell Death via p53 |
title | Depletion of CTCF in Breast Cancer Cells Selectively Induces Cancer Cell Death via p53 |
title_full | Depletion of CTCF in Breast Cancer Cells Selectively Induces Cancer Cell Death via p53 |
title_fullStr | Depletion of CTCF in Breast Cancer Cells Selectively Induces Cancer Cell Death via p53 |
title_full_unstemmed | Depletion of CTCF in Breast Cancer Cells Selectively Induces Cancer Cell Death via p53 |
title_short | Depletion of CTCF in Breast Cancer Cells Selectively Induces Cancer Cell Death via p53 |
title_sort | depletion of ctcf in breast cancer cells selectively induces cancer cell death via p53 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559975/ https://www.ncbi.nlm.nih.gov/pubmed/28819414 http://dx.doi.org/10.7150/jca.18818 |
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