Real-time methylomic aberrations during initiation and progression of induced human mammary epithelial cell tumorigenesis
Neoplastic transformation provides one of the few existing opportunities to analyze molecular changes in real time during the initiation and progression of breast cancer. Human mammary epithelial cells underwent neoplastic reprogramming, generating one line of semitransformed, premalignant cells and...
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| Veröffentlicht in: | Epigenomics 2013-04, Vol.5 (2), p.155-165 |
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| creator | Mitchell, Natalie E Wilson, MacKenzie L Bray, Molly S Crossman, David K Tollefsbol, Trygve O |
| description | Neoplastic transformation provides one of the few existing opportunities to analyze molecular changes in real time during the initiation and progression of breast cancer.
Human mammary epithelial cells underwent neoplastic reprogramming, generating one line of semitransformed, premalignant cells and two separate, temporal lines of fully transformed human mammary epithelial cells (THMECs). An Illumina Infinium HumanMethylation27 BeadChip was used to analyze DNA methylation alterations in 27,578 CpG loci at three consecutive time points over an 80-day (d) transformation period.
The mean value for semitransformed human mammary epithelial cells CpG loci (0.245) was much greater than for either THMEC-40d (0.055) or THMEC-80d (0.066), indicating a large loss of methylation after neoplastic induction. In addition, 54% of CpG loci were hypermethylated during the THMEC-40d to THMEC-80d transition. We observed that the CpG loci exhibiting DNA methylation changes during early oncogenesis were enriched for biological functions like cellular movement; this was distinctly different than in the later, more progressive stages of the transformation process enriched for processes involving differentiation.
The timing of major methylomic changes may be important in directing the cell toward a more cancerous phenotype. In addition, gene-specific hypermethylation appears to silence developmentally related genes, leading to dedifferentiation. |
| doi_str_mv | 10.2217/epi.13.6 |
| format | Article |
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Human mammary epithelial cells underwent neoplastic reprogramming, generating one line of semitransformed, premalignant cells and two separate, temporal lines of fully transformed human mammary epithelial cells (THMECs). An Illumina Infinium HumanMethylation27 BeadChip was used to analyze DNA methylation alterations in 27,578 CpG loci at three consecutive time points over an 80-day (d) transformation period.
The mean value for semitransformed human mammary epithelial cells CpG loci (0.245) was much greater than for either THMEC-40d (0.055) or THMEC-80d (0.066), indicating a large loss of methylation after neoplastic induction. In addition, 54% of CpG loci were hypermethylated during the THMEC-40d to THMEC-80d transition. We observed that the CpG loci exhibiting DNA methylation changes during early oncogenesis were enriched for biological functions like cellular movement; this was distinctly different than in the later, more progressive stages of the transformation process enriched for processes involving differentiation.
The timing of major methylomic changes may be important in directing the cell toward a more cancerous phenotype. In addition, gene-specific hypermethylation appears to silence developmentally related genes, leading to dedifferentiation.</description><identifier>ISSN: 1750-1911</identifier><identifier>EISSN: 1750-192X</identifier><identifier>DOI: 10.2217/epi.13.6</identifier><identifier>PMID: 23566093</identifier><language>eng</language><publisher>England: Future Medicine Ltd</publisher><subject>Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Cell Dedifferentiation ; Cell Line, Tumor ; Cell Transformation, Neoplastic - genetics ; Cellular Reprogramming ; CpG Islands - genetics ; Development and progression ; DNA damage ; DNA methylation ; DNA Methylation - genetics ; Epigenesis, Genetic - genetics ; epigenetics ; Epithelial cells ; Female ; Genetic aspects ; Genome, Human ; Humans ; Illumina Infinium HumanMethylation27 BeadChip ; Mammary Glands, Human - pathology ; neoplastic reprogramming</subject><ispartof>Epigenomics, 2013-04, Vol.5 (2), p.155-165</ispartof><rights>COPYRIGHT 2013 Future Medicine Ltd.</rights><rights>2013 Future Medicine Ltd</rights><rights>2013 Future Medicine Ltd 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c578t-880bf854e9ab72def5d1dd734e06fe030573062748547a5f11406f2850fe97ea3</citedby><cites>FETCH-LOGICAL-c578t-880bf854e9ab72def5d1dd734e06fe030573062748547a5f11406f2850fe97ea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1324570121/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$H</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1324570121?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,778,782,883,21372,27907,27908,33513,43642,64366,64370,72220,73855</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23566093$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mitchell, Natalie E</creatorcontrib><creatorcontrib>Wilson, MacKenzie L</creatorcontrib><creatorcontrib>Bray, Molly S</creatorcontrib><creatorcontrib>Crossman, David K</creatorcontrib><creatorcontrib>Tollefsbol, Trygve O</creatorcontrib><title>Real-time methylomic aberrations during initiation and progression of induced human mammary epithelial cell tumorigenesis</title><title>Epigenomics</title><addtitle>Epigenomics</addtitle><description>Neoplastic transformation provides one of the few existing opportunities to analyze molecular changes in real time during the initiation and progression of breast cancer.
Human mammary epithelial cells underwent neoplastic reprogramming, generating one line of semitransformed, premalignant cells and two separate, temporal lines of fully transformed human mammary epithelial cells (THMECs). An Illumina Infinium HumanMethylation27 BeadChip was used to analyze DNA methylation alterations in 27,578 CpG loci at three consecutive time points over an 80-day (d) transformation period.
The mean value for semitransformed human mammary epithelial cells CpG loci (0.245) was much greater than for either THMEC-40d (0.055) or THMEC-80d (0.066), indicating a large loss of methylation after neoplastic induction. In addition, 54% of CpG loci were hypermethylated during the THMEC-40d to THMEC-80d transition. We observed that the CpG loci exhibiting DNA methylation changes during early oncogenesis were enriched for biological functions like cellular movement; this was distinctly different than in the later, more progressive stages of the transformation process enriched for processes involving differentiation.
The timing of major methylomic changes may be important in directing the cell toward a more cancerous phenotype. In addition, gene-specific hypermethylation appears to silence developmentally related genes, leading to dedifferentiation.</description><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Dedifferentiation</subject><subject>Cell Line, Tumor</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cellular Reprogramming</subject><subject>CpG Islands - genetics</subject><subject>Development and progression</subject><subject>DNA damage</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>Epigenesis, Genetic - genetics</subject><subject>epigenetics</subject><subject>Epithelial cells</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genome, Human</subject><subject>Humans</subject><subject>Illumina Infinium HumanMethylation27 BeadChip</subject><subject>Mammary Glands, Human - pathology</subject><subject>neoplastic reprogramming</subject><issn>1750-1911</issn><issn>1750-192X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkduKFDEQhoMo7jIu-AQS8MabHnPodLpvhGXxBAuCKHgXMkllJksnGZO0MG9vxllHF00ISVV9VfypQug5JWvGqHwNe7-mfD08QpdUCtLRiX17fH5TeoGuSrkjbXE2TgN9ii4YF8NAJn6JDp9Bz131AXCAujvMKXiD9QZy1tWnWLBdso9b7KOv_pcL62jxPqdthlKOdnItahcDFu-WoCMOOgSdD7gpqzuYvZ6xgXnGdQkp-y1EKL48Q0-cngtc3d8r9PXd2y83H7rbT-8_3lzfdkbIsXbjSDZuFD1MeiOZBScstVbyHsjggHAiJCcDk31jpBaO0r4F2CiIg0mC5iv05lR3v2wCWAOxZj2rffZHjSpprx5Got-pbfqh-DjxsZ0VenlfIKfvC5Sq7tKSY9OsKGe9kIQy-ofa6hmUjy61Yib4YtQ1Z4ITyQfWqPV_qLYttL6nCM43_4OEV6cEk1MpGdxZOCXqOH7Vmtx0qKGhL_7-6Bn8PewG9CfALXVpwzMeogF1slqGNz7Cv3V_AmUivzQ</recordid><startdate>20130401</startdate><enddate>20130401</enddate><creator>Mitchell, Natalie E</creator><creator>Wilson, MacKenzie L</creator><creator>Bray, Molly S</creator><creator>Crossman, David K</creator><creator>Tollefsbol, Trygve O</creator><general>Future Medicine Ltd</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>EHMNL</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20130401</creationdate><title>Real-time methylomic aberrations during initiation and progression of induced human mammary epithelial cell tumorigenesis</title><author>Mitchell, Natalie E ; Wilson, MacKenzie L ; Bray, Molly S ; Crossman, David K ; Tollefsbol, Trygve O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c578t-880bf854e9ab72def5d1dd734e06fe030573062748547a5f11406f2850fe97ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell Dedifferentiation</topic><topic>Cell Line, Tumor</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Cellular Reprogramming</topic><topic>CpG Islands - genetics</topic><topic>Development and progression</topic><topic>DNA damage</topic><topic>DNA methylation</topic><topic>DNA Methylation - genetics</topic><topic>Epigenesis, Genetic - genetics</topic><topic>epigenetics</topic><topic>Epithelial cells</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Genome, Human</topic><topic>Humans</topic><topic>Illumina Infinium HumanMethylation27 BeadChip</topic><topic>Mammary Glands, Human - pathology</topic><topic>neoplastic reprogramming</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mitchell, Natalie E</creatorcontrib><creatorcontrib>Wilson, MacKenzie L</creatorcontrib><creatorcontrib>Bray, Molly S</creatorcontrib><creatorcontrib>Crossman, David K</creatorcontrib><creatorcontrib>Tollefsbol, Trygve O</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>UK & Ireland Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</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>PubMed Central (Full Participant titles)</collection><jtitle>Epigenomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mitchell, Natalie E</au><au>Wilson, MacKenzie L</au><au>Bray, Molly S</au><au>Crossman, David K</au><au>Tollefsbol, Trygve O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Real-time methylomic aberrations during initiation and progression of induced human mammary epithelial cell tumorigenesis</atitle><jtitle>Epigenomics</jtitle><addtitle>Epigenomics</addtitle><date>2013-04-01</date><risdate>2013</risdate><volume>5</volume><issue>2</issue><spage>155</spage><epage>165</epage><pages>155-165</pages><issn>1750-1911</issn><eissn>1750-192X</eissn><abstract>Neoplastic transformation provides one of the few existing opportunities to analyze molecular changes in real time during the initiation and progression of breast cancer.
Human mammary epithelial cells underwent neoplastic reprogramming, generating one line of semitransformed, premalignant cells and two separate, temporal lines of fully transformed human mammary epithelial cells (THMECs). An Illumina Infinium HumanMethylation27 BeadChip was used to analyze DNA methylation alterations in 27,578 CpG loci at three consecutive time points over an 80-day (d) transformation period.
The mean value for semitransformed human mammary epithelial cells CpG loci (0.245) was much greater than for either THMEC-40d (0.055) or THMEC-80d (0.066), indicating a large loss of methylation after neoplastic induction. In addition, 54% of CpG loci were hypermethylated during the THMEC-40d to THMEC-80d transition. We observed that the CpG loci exhibiting DNA methylation changes during early oncogenesis were enriched for biological functions like cellular movement; this was distinctly different than in the later, more progressive stages of the transformation process enriched for processes involving differentiation.
The timing of major methylomic changes may be important in directing the cell toward a more cancerous phenotype. In addition, gene-specific hypermethylation appears to silence developmentally related genes, leading to dedifferentiation.</abstract><cop>England</cop><pub>Future Medicine Ltd</pub><pmid>23566093</pmid><doi>10.2217/epi.13.6</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Breast cancer Breast Neoplasms - genetics Breast Neoplasms - pathology Cell Dedifferentiation Cell Line, Tumor Cell Transformation, Neoplastic - genetics Cellular Reprogramming CpG Islands - genetics Development and progression DNA damage DNA methylation DNA Methylation - genetics Epigenesis, Genetic - genetics epigenetics Epithelial cells Female Genetic aspects Genome, Human Humans Illumina Infinium HumanMethylation27 BeadChip Mammary Glands, Human - pathology neoplastic reprogramming |
| title | Real-time methylomic aberrations during initiation and progression of induced human mammary epithelial cell tumorigenesis |
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