ESTABLISHMENT OF THREE HUMAN BREAST EPITHELIAL CELL LINES DERIVED FROM CARRIERS OF THE 999del5 BRCA2 ICELANDIC FOUNDER MUTATION
Germ line mutations in BRCA1 and BRCA2 account for a large proportion of inherited breast and ovarian cancer. Both genes are involved in DNA repair by homologous recombination and are thought to play a vital role in maintaining genomic stability. A major drawback for long-term functional studies of...
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creator | RUBNER FRIDRIKSDOTTIR, AGLA J GUDJONSSON, THORARINN HALLDORSSON, THORHALLUR BJÖRNSSON, JOHANNES STEINARSDOTTIR, MARGRET JOHANNSSON, OSKAR THOR ÖGMUNDSDOTTIR, HELGA M |
description | Germ line mutations in BRCA1 and BRCA2 account for a large proportion of inherited breast and ovarian cancer. Both genes are involved in DNA repair by homologous recombination and are thought to play a vital role in maintaining genomic stability. A major drawback for long-term functional studies of BRCA in general and BRCA2 in particular has been a lack of representative human breast epithelial cell lines. In the present study, we have established three cell lines from two patients harboring the 999del5 germ line founder mutation in the BRCA2 gene. Primary cultures were established from cellular outgrowth of explanted tissue and subsequently transfected with a retroviral construct containing the HPV-16 E6 and E7 oncogenes. Paired cancer-derived and normal-derived cell lines were established from one patient referred to as BRCA2-999del5-2T and BRCA2-999del5-2N, respectively. In addition, one cell line was derived from cancer-associated normal tissue from another patient referred to as BRCA2-999del5-1N. All three cell lines showed characteristics of breast epithelial cells as evidenced by expression of breast epithelial specific cytokeratins. Cytogenetic analysis showed marked chromosomal instability with tetraploidy and frequent telomeric associations. In conclusion, we have established three breast epithelial cell lines from two patients carrying the BRCA2 Icelandic 999del5 founder mutation. These cell lines form the basis for further studies on carcinogenesis and malignant progression of breast cancer on a defined genetic background. |
doi_str_mv | 10.1290/0505033.1 |
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Both genes are involved in DNA repair by homologous recombination and are thought to play a vital role in maintaining genomic stability. A major drawback for long-term functional studies of BRCA in general and BRCA2 in particular has been a lack of representative human breast epithelial cell lines. In the present study, we have established three cell lines from two patients harboring the 999del5 germ line founder mutation in the BRCA2 gene. Primary cultures were established from cellular outgrowth of explanted tissue and subsequently transfected with a retroviral construct containing the HPV-16 E6 and E7 oncogenes. Paired cancer-derived and normal-derived cell lines were established from one patient referred to as BRCA2-999del5-2T and BRCA2-999del5-2N, respectively. In addition, one cell line was derived from cancer-associated normal tissue from another patient referred to as BRCA2-999del5-1N. All three cell lines showed characteristics of breast epithelial cells as evidenced by expression of breast epithelial specific cytokeratins. Cytogenetic analysis showed marked chromosomal instability with tetraploidy and frequent telomeric associations. In conclusion, we have established three breast epithelial cell lines from two patients carrying the BRCA2 Icelandic 999del5 founder mutation. These cell lines form the basis for further studies on carcinogenesis and malignant progression of breast cancer on a defined genetic background.</description><identifier>ISSN: 1071-2690</identifier><identifier>ISSN: 1543-706X</identifier><identifier>EISSN: 1543-706X</identifier><identifier>DOI: 10.1290/0505033.1</identifier><identifier>PMID: 16448223</identifier><identifier>CODEN: IVCAED</identifier><language>eng</language><publisher>Germany: Society for In Vitro Biology</publisher><subject>BRCA2 mutation ; Breast - cytology ; Breast cancer ; CELL AND TISSUE MODELS ; Cell Line, Tumor ; Cell lines ; Chromosomal Instability - genetics ; Cultured cells ; Cytogenetic Analysis ; DNA Mutational Analysis ; DNA Primers ; Epithelial cells ; Epithelial Cells - cytology ; Exons ; Female ; Genes, BRCA2 ; Genetic mutation ; Genetic Vectors - genetics ; Humans ; Iceland ; immortalization ; Immunohistochemistry ; Karyotyping ; Keratins - metabolism ; Mutation - genetics ; Oncogenes - genetics ; Retroviridae ; Stem cells ; Tumor cell line ; Tumor stem cells ; Tumors</subject><ispartof>In vitro cellular & developmental biology. Animal, 2005-11, Vol.41 (10), p.337-342</ispartof><rights>Society for In Vitro Biology</rights><rights>Copyright 2005 Society for In Vitro Biology</rights><rights>Copyright Society for In Vitro Biology Nov/Dec 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b394t-a4cb51b275191faec00d5d9a8e0c88f9c9228c1f3f0875eb777fbfaae84b43123</citedby><cites>FETCH-LOGICAL-b394t-a4cb51b275191faec00d5d9a8e0c88f9c9228c1f3f0875eb777fbfaae84b43123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://bioone.org/doi/pdf/10.1290/0505033.1$$EPDF$$P50$$Gbioone$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/4295645$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,777,781,800,26959,27905,27906,52344,57998,58231</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16448223$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>RUBNER FRIDRIKSDOTTIR, AGLA J</creatorcontrib><creatorcontrib>GUDJONSSON, THORARINN</creatorcontrib><creatorcontrib>HALLDORSSON, THORHALLUR</creatorcontrib><creatorcontrib>BJÖRNSSON, JOHANNES</creatorcontrib><creatorcontrib>STEINARSDOTTIR, MARGRET</creatorcontrib><creatorcontrib>JOHANNSSON, OSKAR THOR</creatorcontrib><creatorcontrib>ÖGMUNDSDOTTIR, HELGA M</creatorcontrib><title>ESTABLISHMENT OF THREE HUMAN BREAST EPITHELIAL CELL LINES DERIVED FROM CARRIERS OF THE 999del5 BRCA2 ICELANDIC FOUNDER MUTATION</title><title>In vitro cellular & developmental biology. Animal</title><addtitle>In Vitro Cell Dev Biol Anim</addtitle><description>Germ line mutations in BRCA1 and BRCA2 account for a large proportion of inherited breast and ovarian cancer. Both genes are involved in DNA repair by homologous recombination and are thought to play a vital role in maintaining genomic stability. A major drawback for long-term functional studies of BRCA in general and BRCA2 in particular has been a lack of representative human breast epithelial cell lines. In the present study, we have established three cell lines from two patients harboring the 999del5 germ line founder mutation in the BRCA2 gene. Primary cultures were established from cellular outgrowth of explanted tissue and subsequently transfected with a retroviral construct containing the HPV-16 E6 and E7 oncogenes. Paired cancer-derived and normal-derived cell lines were established from one patient referred to as BRCA2-999del5-2T and BRCA2-999del5-2N, respectively. In addition, one cell line was derived from cancer-associated normal tissue from another patient referred to as BRCA2-999del5-1N. All three cell lines showed characteristics of breast epithelial cells as evidenced by expression of breast epithelial specific cytokeratins. Cytogenetic analysis showed marked chromosomal instability with tetraploidy and frequent telomeric associations. In conclusion, we have established three breast epithelial cell lines from two patients carrying the BRCA2 Icelandic 999del5 founder mutation. These cell lines form the basis for further studies on carcinogenesis and malignant progression of breast cancer on a defined genetic background.</description><subject>BRCA2 mutation</subject><subject>Breast - cytology</subject><subject>Breast cancer</subject><subject>CELL AND TISSUE MODELS</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Chromosomal Instability - genetics</subject><subject>Cultured cells</subject><subject>Cytogenetic Analysis</subject><subject>DNA Mutational Analysis</subject><subject>DNA Primers</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - cytology</subject><subject>Exons</subject><subject>Female</subject><subject>Genes, BRCA2</subject><subject>Genetic mutation</subject><subject>Genetic Vectors - genetics</subject><subject>Humans</subject><subject>Iceland</subject><subject>immortalization</subject><subject>Immunohistochemistry</subject><subject>Karyotyping</subject><subject>Keratins - metabolism</subject><subject>Mutation - genetics</subject><subject>Oncogenes - genetics</subject><subject>Retroviridae</subject><subject>Stem cells</subject><subject>Tumor cell line</subject><subject>Tumor stem cells</subject><subject>Tumors</subject><issn>1071-2690</issn><issn>1543-706X</issn><issn>1543-706X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</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>eNp9kc9r2zAcxcXoWLt2h91LETus9OBOPy3rqDpKLXDsYTujN2M7MiQkcWclh532r1fFoYMdKh30hfd57yt4AHzF6B4TiX4g7i-l9_gDuMCc0UCg8OnMz0jggIQSnYPPzm2QPxKHn8A5DhmLCKEX4K8uK_WQmjJZ6KyC-RxWSaE1TJYLlcGHQquygvqnqRKdGpXCWKcpTE2mSzjThfmlZ3Be5AsYq6IwuiinBA2llCu75T4hVgQab1PZzMRwni8zb4SLZaUqk2dX4GPfbJ39cnovwXKuqzgJ0vzRxCoNWirZIWhY13LcEsGxxH1jO4RWfCWbyKIuinrZSUKiDve0R5HgthVC9G3fNDZiLaOY0Evwfcp9HoffR-sO9W7tOrvdNns7HF1NEKIcY-HBb_-Bm-E47v3fakKZFJgg5qG7CerGwbnR9vXzuN41458ao_q1kvpUSY09e3MKPLY7u_pHnjrwwPUEbNxhGN90RiQPGffy7SS362HY23c2vQCEHY97</recordid><startdate>20051101</startdate><enddate>20051101</enddate><creator>RUBNER FRIDRIKSDOTTIR, AGLA J</creator><creator>GUDJONSSON, THORARINN</creator><creator>HALLDORSSON, THORHALLUR</creator><creator>BJÖRNSSON, JOHANNES</creator><creator>STEINARSDOTTIR, MARGRET</creator><creator>JOHANNSSON, OSKAR THOR</creator><creator>ÖGMUNDSDOTTIR, HELGA M</creator><general>Society for In Vitro Biology</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>4T-</scope><scope>7QL</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</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>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7QO</scope><scope>RC3</scope></search><sort><creationdate>20051101</creationdate><title>ESTABLISHMENT OF THREE HUMAN BREAST EPITHELIAL CELL LINES DERIVED FROM CARRIERS OF THE 999del5 BRCA2 ICELANDIC FOUNDER MUTATION</title><author>RUBNER FRIDRIKSDOTTIR, AGLA J ; GUDJONSSON, THORARINN ; HALLDORSSON, THORHALLUR ; BJÖRNSSON, JOHANNES ; STEINARSDOTTIR, MARGRET ; JOHANNSSON, OSKAR THOR ; ÖGMUNDSDOTTIR, HELGA M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b394t-a4cb51b275191faec00d5d9a8e0c88f9c9228c1f3f0875eb777fbfaae84b43123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>BRCA2 mutation</topic><topic>Breast - cytology</topic><topic>Breast cancer</topic><topic>CELL AND TISSUE MODELS</topic><topic>Cell Line, Tumor</topic><topic>Cell lines</topic><topic>Chromosomal Instability - genetics</topic><topic>Cultured cells</topic><topic>Cytogenetic Analysis</topic><topic>DNA Mutational Analysis</topic><topic>DNA Primers</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - cytology</topic><topic>Exons</topic><topic>Female</topic><topic>Genes, BRCA2</topic><topic>Genetic mutation</topic><topic>Genetic Vectors - genetics</topic><topic>Humans</topic><topic>Iceland</topic><topic>immortalization</topic><topic>Immunohistochemistry</topic><topic>Karyotyping</topic><topic>Keratins - metabolism</topic><topic>Mutation - genetics</topic><topic>Oncogenes - genetics</topic><topic>Retroviridae</topic><topic>Stem cells</topic><topic>Tumor cell line</topic><topic>Tumor stem cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>RUBNER FRIDRIKSDOTTIR, AGLA J</creatorcontrib><creatorcontrib>GUDJONSSON, THORARINN</creatorcontrib><creatorcontrib>HALLDORSSON, THORHALLUR</creatorcontrib><creatorcontrib>BJÖRNSSON, JOHANNES</creatorcontrib><creatorcontrib>STEINARSDOTTIR, MARGRET</creatorcontrib><creatorcontrib>JOHANNSSON, OSKAR THOR</creatorcontrib><creatorcontrib>ÖGMUNDSDOTTIR, HELGA M</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>Docstoc</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech 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 One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</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 & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>Biotechnology Research Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>In vitro cellular & developmental biology. Animal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>RUBNER FRIDRIKSDOTTIR, AGLA J</au><au>GUDJONSSON, THORARINN</au><au>HALLDORSSON, THORHALLUR</au><au>BJÖRNSSON, JOHANNES</au><au>STEINARSDOTTIR, MARGRET</au><au>JOHANNSSON, OSKAR THOR</au><au>ÖGMUNDSDOTTIR, HELGA M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ESTABLISHMENT OF THREE HUMAN BREAST EPITHELIAL CELL LINES DERIVED FROM CARRIERS OF THE 999del5 BRCA2 ICELANDIC FOUNDER MUTATION</atitle><jtitle>In vitro cellular & developmental biology. Animal</jtitle><addtitle>In Vitro Cell Dev Biol Anim</addtitle><date>2005-11-01</date><risdate>2005</risdate><volume>41</volume><issue>10</issue><spage>337</spage><epage>342</epage><pages>337-342</pages><issn>1071-2690</issn><issn>1543-706X</issn><eissn>1543-706X</eissn><coden>IVCAED</coden><abstract>Germ line mutations in BRCA1 and BRCA2 account for a large proportion of inherited breast and ovarian cancer. Both genes are involved in DNA repair by homologous recombination and are thought to play a vital role in maintaining genomic stability. A major drawback for long-term functional studies of BRCA in general and BRCA2 in particular has been a lack of representative human breast epithelial cell lines. In the present study, we have established three cell lines from two patients harboring the 999del5 germ line founder mutation in the BRCA2 gene. Primary cultures were established from cellular outgrowth of explanted tissue and subsequently transfected with a retroviral construct containing the HPV-16 E6 and E7 oncogenes. Paired cancer-derived and normal-derived cell lines were established from one patient referred to as BRCA2-999del5-2T and BRCA2-999del5-2N, respectively. In addition, one cell line was derived from cancer-associated normal tissue from another patient referred to as BRCA2-999del5-1N. All three cell lines showed characteristics of breast epithelial cells as evidenced by expression of breast epithelial specific cytokeratins. Cytogenetic analysis showed marked chromosomal instability with tetraploidy and frequent telomeric associations. In conclusion, we have established three breast epithelial cell lines from two patients carrying the BRCA2 Icelandic 999del5 founder mutation. These cell lines form the basis for further studies on carcinogenesis and malignant progression of breast cancer on a defined genetic background.</abstract><cop>Germany</cop><pub>Society for In Vitro Biology</pub><pmid>16448223</pmid><doi>10.1290/0505033.1</doi><tpages>6</tpages></addata></record> |
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subjects | BRCA2 mutation Breast - cytology Breast cancer CELL AND TISSUE MODELS Cell Line, Tumor Cell lines Chromosomal Instability - genetics Cultured cells Cytogenetic Analysis DNA Mutational Analysis DNA Primers Epithelial cells Epithelial Cells - cytology Exons Female Genes, BRCA2 Genetic mutation Genetic Vectors - genetics Humans Iceland immortalization Immunohistochemistry Karyotyping Keratins - metabolism Mutation - genetics Oncogenes - genetics Retroviridae Stem cells Tumor cell line Tumor stem cells Tumors |
title | ESTABLISHMENT OF THREE HUMAN BREAST EPITHELIAL CELL LINES DERIVED FROM CARRIERS OF THE 999del5 BRCA2 ICELANDIC FOUNDER MUTATION |
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