Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers

Aberrant cytosine methylation affects regulation of hundreds of genes during cancer development. In this study, a novel aberrantly hypermethylated CpG island in cancer was discovered within the TOX2 promoter. TOX2 was unmethylated in normal cells but 28% lung (n = 190) and 23% breast (n = 80) tumors...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2012-04, Vol.7 (4), p.e34850
Main Authors: Tessema, Mathewos, Yingling, Christin M, Grimes, Marcie J, Thomas, Cynthia L, Liu, Yushi, Leng, Shuguang, Joste, Nancy, Belinsky, Steven A
Format: Article
Language:English
Subjects:
Aberration
Apoptosis Regulatory Proteins
Base Sequence
Biology
Breast cancer
Breast Neoplasms - genetics
Cancer
Cancer genetics
Carcinogenesis
Carcinogens
Cell adhesion & migration
Cell differentiation
Chromosomal proteins
CpG Islands
Cytosine
Deactivation
Deoxyribonucleic acid
Differentiation (biology)
DNA
DNA Methylation
DNA repair
Epigenesis, Genetic
Epigenetic inheritance
Epigenetics
Female
Gangrene
Gene expression
Gene Expression Regulation, Neoplastic
Gene regulation
Genes
Genetic aspects
Genetic research
Genomes
Genomics
High Mobility Group Proteins - genetics
Histology
HMGB Proteins - genetics
Homology
Humans
Inactivation
Inflammation
Inflammatory response
Lung - drug effects
Lung - metabolism
Lung cancer
Lung diseases
Lung Neoplasms - genetics
Male
Medicine
Methylation
Molecular Sequence Data
Neoplasm Proteins - genetics
Protein structure
Proteins
Receptors, Progesterone - genetics
Sequence Analysis, DNA
siRNA
Smoking
Studies
Trans-Activators
Transcription factors
Tumors
Womens health
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c758t-aec75299fe4622b89eeaaade31d20702a463aba47305c0ab852ba8015212166b3
cites cdi_FETCH-LOGICAL-c758t-aec75299fe4622b89eeaaade31d20702a463aba47305c0ab852ba8015212166b3
container_end_page
container_issue 4
container_start_page e34850
container_title PloS one
container_volume 7
creator Tessema, Mathewos
Yingling, Christin M
Grimes, Marcie J
Thomas, Cynthia L
Liu, Yushi
Leng, Shuguang
Joste, Nancy
Belinsky, Steven A
description Aberrant cytosine methylation affects regulation of hundreds of genes during cancer development. In this study, a novel aberrantly hypermethylated CpG island in cancer was discovered within the TOX2 promoter. TOX2 was unmethylated in normal cells but 28% lung (n = 190) and 23% breast (n = 80) tumors were methylated. Expression of two novel TOX2 transcripts identified was significantly reduced in primary lung tumors than distant normal lung (p
doi_str_mv 10.1371/journal.pone.0034850
format article
fullrecord <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1340941147</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A477149761</galeid><doaj_id>oai_doaj_org_article_040418ab3a7d45e6acca775a027769b3</doaj_id><sourcerecordid>A477149761</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-aec75299fe4622b89eeaaade31d20702a463aba47305c0ab852ba8015212166b3</originalsourceid><addsrcrecordid>eNqNkl2L1DAYhYso7jr6D0QDguDFjPlq0t4Iy_o1sDCgq3gX3rRpJ0vajEkrO__ejNNdpqAguUh485yTcDhZ9pzgFWGSvL3xY-jBrXa-NyuMGS9y_CA7JyWjS0Exe3hyPsuexHiDcc4KIR5nZ5TyUhQSn2fuvW0aE0w_WHDI7GxrejPYCgXTjg4G63vkG3S9-YHiqBvorNujrW23qPPaOjvsURv8uEPa36KDNiLbIzf2LYK-RjoYiAOqoK9MiE-zRw24aJ5N-yL79vHD9eXn5dXm0_ry4mpZybwYlmDSTsuyMVxQqovSGACoDSM1xRJT4IKBBi4ZzisMusiphgKTnBJKhNBskb08-u6cj2oKKirCOC45IUm4yNZHovZwo3bBdhD2yoNVfwY-tApCisEZhTnmpADNQNY8NwKqCqTMAVMpRalZ8no3vTbqztRVyjKAm5nOb3q7Va3_pRgjpcA0GbyaDIL_OZo4_OPLE9VC-pXtG5_Mqs7GSl1wKQkvpSCJWv2FSqs2na1SVRqb5jPBm5kgMYO5HVoYY1Trr1_-n918n7OvT9itATdso3fjoVFxDvIjWAUfYzDNfXIEq0PT79JQh6arqelJ9uI09XvRXbXZbxCW-Uw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1340941147</pqid></control><display><type>article</type><title>Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers</title><source>Publicly Available Content (ProQuest)</source><source>PubMed Central</source><creator>Tessema, Mathewos ; Yingling, Christin M ; Grimes, Marcie J ; Thomas, Cynthia L ; Liu, Yushi ; Leng, Shuguang ; Joste, Nancy ; Belinsky, Steven A</creator><contributor>Tao, Qian</contributor><creatorcontrib>Tessema, Mathewos ; Yingling, Christin M ; Grimes, Marcie J ; Thomas, Cynthia L ; Liu, Yushi ; Leng, Shuguang ; Joste, Nancy ; Belinsky, Steven A ; Tao, Qian</creatorcontrib><description>Aberrant cytosine methylation affects regulation of hundreds of genes during cancer development. In this study, a novel aberrantly hypermethylated CpG island in cancer was discovered within the TOX2 promoter. TOX2 was unmethylated in normal cells but 28% lung (n = 190) and 23% breast (n = 80) tumors were methylated. Expression of two novel TOX2 transcripts identified was significantly reduced in primary lung tumors than distant normal lung (p&lt;0.05). These transcripts were silenced in methylated lung and breast cancer cells and 5-Aza-2-deoxycytidine treatment re-expressed both. Extension of these assays to TOX, TOX3, and TOX4 genes that share similar genomic structure and protein homology with TOX2 revealed distinct methylation profiles by smoking status, histology, and cancer type. TOX was almost exclusively methylated in breast (43%) than lung (5%) cancer, whereas TOX3 was frequently methylated in lung (58%) than breast (30%) tumors. TOX4 was unmethylated in all samples and showed the highest expression in normal lung. Compared to TOX4, expression of TOX, TOX2 and TOX3 in normal lung was 25, 44, and 88% lower, respectively, supporting the premise that reduced promoter activity confers increased susceptibility to methylation during lung carcinogenesis. Genome-wide assays revealed that siRNA-mediated TOX2 knockdown modulated multiple pathways while TOX3 inactivation targeted neuronal development and function. Although these knockdowns did not result in further phenotypic changes of lung cancer cells in vitro, the impact on tissue remodeling, inflammatory response, and cell differentiation pathways suggest a potential role for TOX2 in modulating tumor microenvironment.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0034850</identifier><identifier>PMID: 22496870</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Apoptosis Regulatory Proteins ; Base Sequence ; Biology ; Breast cancer ; Breast Neoplasms - genetics ; Cancer ; Cancer genetics ; Carcinogenesis ; Carcinogens ; Cell adhesion &amp; migration ; Cell differentiation ; Chromosomal proteins ; CpG Islands ; Cytosine ; Deactivation ; Deoxyribonucleic acid ; Differentiation (biology) ; DNA ; DNA Methylation ; DNA repair ; Epigenesis, Genetic ; Epigenetic inheritance ; Epigenetics ; Female ; Gangrene ; Gene expression ; Gene Expression Regulation, Neoplastic ; Gene regulation ; Genes ; Genetic aspects ; Genetic research ; Genomes ; Genomics ; High Mobility Group Proteins - genetics ; Histology ; HMGB Proteins - genetics ; Homology ; Humans ; Inactivation ; Inflammation ; Inflammatory response ; Lung - drug effects ; Lung - metabolism ; Lung cancer ; Lung diseases ; Lung Neoplasms - genetics ; Male ; Medicine ; Methylation ; Molecular Sequence Data ; Neoplasm Proteins - genetics ; Protein structure ; Proteins ; Receptors, Progesterone - genetics ; Sequence Analysis, DNA ; siRNA ; Smoking ; Studies ; Trans-Activators ; Transcription factors ; Tumors ; Womens health</subject><ispartof>PloS one, 2012-04, Vol.7 (4), p.e34850</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Tessema et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Tessema et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-aec75299fe4622b89eeaaade31d20702a463aba47305c0ab852ba8015212166b3</citedby><cites>FETCH-LOGICAL-c758t-aec75299fe4622b89eeaaade31d20702a463aba47305c0ab852ba8015212166b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1340941147/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1340941147?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25731,27901,27902,36989,44566,53766,53768,74869</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22496870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tao, Qian</contributor><creatorcontrib>Tessema, Mathewos</creatorcontrib><creatorcontrib>Yingling, Christin M</creatorcontrib><creatorcontrib>Grimes, Marcie J</creatorcontrib><creatorcontrib>Thomas, Cynthia L</creatorcontrib><creatorcontrib>Liu, Yushi</creatorcontrib><creatorcontrib>Leng, Shuguang</creatorcontrib><creatorcontrib>Joste, Nancy</creatorcontrib><creatorcontrib>Belinsky, Steven A</creatorcontrib><title>Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Aberrant cytosine methylation affects regulation of hundreds of genes during cancer development. In this study, a novel aberrantly hypermethylated CpG island in cancer was discovered within the TOX2 promoter. TOX2 was unmethylated in normal cells but 28% lung (n = 190) and 23% breast (n = 80) tumors were methylated. Expression of two novel TOX2 transcripts identified was significantly reduced in primary lung tumors than distant normal lung (p&lt;0.05). These transcripts were silenced in methylated lung and breast cancer cells and 5-Aza-2-deoxycytidine treatment re-expressed both. Extension of these assays to TOX, TOX3, and TOX4 genes that share similar genomic structure and protein homology with TOX2 revealed distinct methylation profiles by smoking status, histology, and cancer type. TOX was almost exclusively methylated in breast (43%) than lung (5%) cancer, whereas TOX3 was frequently methylated in lung (58%) than breast (30%) tumors. TOX4 was unmethylated in all samples and showed the highest expression in normal lung. Compared to TOX4, expression of TOX, TOX2 and TOX3 in normal lung was 25, 44, and 88% lower, respectively, supporting the premise that reduced promoter activity confers increased susceptibility to methylation during lung carcinogenesis. Genome-wide assays revealed that siRNA-mediated TOX2 knockdown modulated multiple pathways while TOX3 inactivation targeted neuronal development and function. Although these knockdowns did not result in further phenotypic changes of lung cancer cells in vitro, the impact on tissue remodeling, inflammatory response, and cell differentiation pathways suggest a potential role for TOX2 in modulating tumor microenvironment.</description><subject>Aberration</subject><subject>Apoptosis Regulatory Proteins</subject><subject>Base Sequence</subject><subject>Biology</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Cancer</subject><subject>Cancer genetics</subject><subject>Carcinogenesis</subject><subject>Carcinogens</subject><subject>Cell adhesion &amp; migration</subject><subject>Cell differentiation</subject><subject>Chromosomal proteins</subject><subject>CpG Islands</subject><subject>Cytosine</subject><subject>Deactivation</subject><subject>Deoxyribonucleic acid</subject><subject>Differentiation (biology)</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>DNA repair</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Gangrene</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic research</subject><subject>Genomes</subject><subject>Genomics</subject><subject>High Mobility Group Proteins - genetics</subject><subject>Histology</subject><subject>HMGB Proteins - genetics</subject><subject>Homology</subject><subject>Humans</subject><subject>Inactivation</subject><subject>Inflammation</subject><subject>Inflammatory response</subject><subject>Lung - drug effects</subject><subject>Lung - metabolism</subject><subject>Lung cancer</subject><subject>Lung diseases</subject><subject>Lung Neoplasms - genetics</subject><subject>Male</subject><subject>Medicine</subject><subject>Methylation</subject><subject>Molecular Sequence Data</subject><subject>Neoplasm Proteins - genetics</subject><subject>Protein structure</subject><subject>Proteins</subject><subject>Receptors, Progesterone - genetics</subject><subject>Sequence Analysis, DNA</subject><subject>siRNA</subject><subject>Smoking</subject><subject>Studies</subject><subject>Trans-Activators</subject><subject>Transcription factors</subject><subject>Tumors</subject><subject>Womens health</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAYhYso7jr6D0QDguDFjPlq0t4Iy_o1sDCgq3gX3rRpJ0vajEkrO__ejNNdpqAguUh485yTcDhZ9pzgFWGSvL3xY-jBrXa-NyuMGS9y_CA7JyWjS0Exe3hyPsuexHiDcc4KIR5nZ5TyUhQSn2fuvW0aE0w_WHDI7GxrejPYCgXTjg4G63vkG3S9-YHiqBvorNujrW23qPPaOjvsURv8uEPa36KDNiLbIzf2LYK-RjoYiAOqoK9MiE-zRw24aJ5N-yL79vHD9eXn5dXm0_ry4mpZybwYlmDSTsuyMVxQqovSGACoDSM1xRJT4IKBBi4ZzisMusiphgKTnBJKhNBskb08-u6cj2oKKirCOC45IUm4yNZHovZwo3bBdhD2yoNVfwY-tApCisEZhTnmpADNQNY8NwKqCqTMAVMpRalZ8no3vTbqztRVyjKAm5nOb3q7Va3_pRgjpcA0GbyaDIL_OZo4_OPLE9VC-pXtG5_Mqs7GSl1wKQkvpSCJWv2FSqs2na1SVRqb5jPBm5kgMYO5HVoYY1Trr1_-n918n7OvT9itATdso3fjoVFxDvIjWAUfYzDNfXIEq0PT79JQh6arqelJ9uI09XvRXbXZbxCW-Uw</recordid><startdate>20120404</startdate><enddate>20120404</enddate><creator>Tessema, Mathewos</creator><creator>Yingling, Christin M</creator><creator>Grimes, Marcie J</creator><creator>Thomas, Cynthia L</creator><creator>Liu, Yushi</creator><creator>Leng, Shuguang</creator><creator>Joste, Nancy</creator><creator>Belinsky, Steven A</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120404</creationdate><title>Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers</title><author>Tessema, Mathewos ; Yingling, Christin M ; Grimes, Marcie J ; Thomas, Cynthia L ; Liu, Yushi ; Leng, Shuguang ; Joste, Nancy ; Belinsky, Steven A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-aec75299fe4622b89eeaaade31d20702a463aba47305c0ab852ba8015212166b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aberration</topic><topic>Apoptosis Regulatory Proteins</topic><topic>Base Sequence</topic><topic>Biology</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Cancer</topic><topic>Cancer genetics</topic><topic>Carcinogenesis</topic><topic>Carcinogens</topic><topic>Cell adhesion &amp; migration</topic><topic>Cell differentiation</topic><topic>Chromosomal proteins</topic><topic>CpG Islands</topic><topic>Cytosine</topic><topic>Deactivation</topic><topic>Deoxyribonucleic acid</topic><topic>Differentiation (biology)</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>DNA repair</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetic inheritance</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Gangrene</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene regulation</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic research</topic><topic>Genomes</topic><topic>Genomics</topic><topic>High Mobility Group Proteins - genetics</topic><topic>Histology</topic><topic>HMGB Proteins - genetics</topic><topic>Homology</topic><topic>Humans</topic><topic>Inactivation</topic><topic>Inflammation</topic><topic>Inflammatory response</topic><topic>Lung - drug effects</topic><topic>Lung - metabolism</topic><topic>Lung cancer</topic><topic>Lung diseases</topic><topic>Lung Neoplasms - genetics</topic><topic>Male</topic><topic>Medicine</topic><topic>Methylation</topic><topic>Molecular Sequence Data</topic><topic>Neoplasm Proteins - genetics</topic><topic>Protein structure</topic><topic>Proteins</topic><topic>Receptors, Progesterone - genetics</topic><topic>Sequence Analysis, DNA</topic><topic>siRNA</topic><topic>Smoking</topic><topic>Studies</topic><topic>Trans-Activators</topic><topic>Transcription factors</topic><topic>Tumors</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tessema, Mathewos</creatorcontrib><creatorcontrib>Yingling, Christin M</creatorcontrib><creatorcontrib>Grimes, Marcie J</creatorcontrib><creatorcontrib>Thomas, Cynthia L</creatorcontrib><creatorcontrib>Liu, Yushi</creatorcontrib><creatorcontrib>Leng, Shuguang</creatorcontrib><creatorcontrib>Joste, Nancy</creatorcontrib><creatorcontrib>Belinsky, Steven A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints In Context</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing &amp; Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (ProQuest Medical &amp; Health Databases)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest advanced technologies &amp; aerospace journals</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals - May need to register for free articles</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tessema, Mathewos</au><au>Yingling, Christin M</au><au>Grimes, Marcie J</au><au>Thomas, Cynthia L</au><au>Liu, Yushi</au><au>Leng, Shuguang</au><au>Joste, Nancy</au><au>Belinsky, Steven A</au><au>Tao, Qian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-04-04</date><risdate>2012</risdate><volume>7</volume><issue>4</issue><spage>e34850</spage><pages>e34850-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Aberrant cytosine methylation affects regulation of hundreds of genes during cancer development. In this study, a novel aberrantly hypermethylated CpG island in cancer was discovered within the TOX2 promoter. TOX2 was unmethylated in normal cells but 28% lung (n = 190) and 23% breast (n = 80) tumors were methylated. Expression of two novel TOX2 transcripts identified was significantly reduced in primary lung tumors than distant normal lung (p&lt;0.05). These transcripts were silenced in methylated lung and breast cancer cells and 5-Aza-2-deoxycytidine treatment re-expressed both. Extension of these assays to TOX, TOX3, and TOX4 genes that share similar genomic structure and protein homology with TOX2 revealed distinct methylation profiles by smoking status, histology, and cancer type. TOX was almost exclusively methylated in breast (43%) than lung (5%) cancer, whereas TOX3 was frequently methylated in lung (58%) than breast (30%) tumors. TOX4 was unmethylated in all samples and showed the highest expression in normal lung. Compared to TOX4, expression of TOX, TOX2 and TOX3 in normal lung was 25, 44, and 88% lower, respectively, supporting the premise that reduced promoter activity confers increased susceptibility to methylation during lung carcinogenesis. Genome-wide assays revealed that siRNA-mediated TOX2 knockdown modulated multiple pathways while TOX3 inactivation targeted neuronal development and function. Although these knockdowns did not result in further phenotypic changes of lung cancer cells in vitro, the impact on tissue remodeling, inflammatory response, and cell differentiation pathways suggest a potential role for TOX2 in modulating tumor microenvironment.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22496870</pmid><doi>10.1371/journal.pone.0034850</doi><tpages>e34850</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2012-04, Vol.7 (4), p.e34850
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1340941147
source Publicly Available Content (ProQuest); PubMed Central
subjects Aberration
Apoptosis Regulatory Proteins
Base Sequence
Biology
Breast cancer
Breast Neoplasms - genetics
Cancer
Cancer genetics
Carcinogenesis
Carcinogens
Cell adhesion & migration
Cell differentiation
Chromosomal proteins
CpG Islands
Cytosine
Deactivation
Deoxyribonucleic acid
Differentiation (biology)
DNA
DNA Methylation
DNA repair
Epigenesis, Genetic
Epigenetic inheritance
Epigenetics
Female
Gangrene
Gene expression
Gene Expression Regulation, Neoplastic
Gene regulation
Genes
Genetic aspects
Genetic research
Genomes
Genomics
High Mobility Group Proteins - genetics
Histology
HMGB Proteins - genetics
Homology
Humans
Inactivation
Inflammation
Inflammatory response
Lung - drug effects
Lung - metabolism
Lung cancer
Lung diseases
Lung Neoplasms - genetics
Male
Medicine
Methylation
Molecular Sequence Data
Neoplasm Proteins - genetics
Protein structure
Proteins
Receptors, Progesterone - genetics
Sequence Analysis, DNA
siRNA
Smoking
Studies
Trans-Activators
Transcription factors
Tumors
Womens health
title Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T02%3A10%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Differential%20epigenetic%20regulation%20of%20TOX%20subfamily%20high%20mobility%20group%20box%20genes%20in%20lung%20and%20breast%20cancers&rft.jtitle=PloS%20one&rft.au=Tessema,%20Mathewos&rft.date=2012-04-04&rft.volume=7&rft.issue=4&rft.spage=e34850&rft.pages=e34850-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0034850&rft_dat=%3Cgale_plos_%3EA477149761%3C/gale_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c758t-aec75299fe4622b89eeaaade31d20702a463aba47305c0ab852ba8015212166b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1340941147&rft_id=info:pmid/22496870&rft_galeid=A477149761&rfr_iscdi=true