Decreased TGF[beta] signaling and increased COX2 expression in high risk women with increased mammographic breast density
High mammographic density is associated with a increased risk of breast cancer. We hypothesized that specific pathways exist that are associated with increased mammographic density, and may therefore be used to identify potential targets for chemoprevention. Histologically confirmed normal breast ti...
Gespeichert in:
| Veröffentlicht in: | Breast cancer research and treatment 2010-01, Vol.119 (2), p.305 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 2 |
| container_start_page | 305 |
| container_title | Breast cancer research and treatment |
| container_volume | 119 |
| creator | Yang, Wei Tse Lewis, Michael T Hess, Kenneth Wong, Helen Tsimelzon, Anna Karadag, Nese Cairo, Michelina Wei, Caimaio Meric-bernstam, Funda Brown, Powel Arun, Banu Hortobagyi, Gabriel N Sahin, Aysegul Chang, Jenny C |
| description | High mammographic density is associated with a increased risk of breast cancer. We hypothesized that specific pathways exist that are associated with increased mammographic density, and may therefore be used to identify potential targets for chemoprevention. Histologically confirmed normal breast tissue was collected from women undergoing breast surgery who had available demographic data and mammograms for review. Women with low versus high mammographic breast density were compared. Differentially expressed genes using Affymetrix HG U133Plus2 chips were identified in dense versus non-dense tissue. Immunohistochemical analysis (IHC) of estrogen receptor, progesterone receptor, Ki67, and COX2 expression was performed. About 66 women were identified, 28 (42%) had high, and 38 (58%) had low mammographic density. About 73 genes had differential expression between normal breast tissue with high and low mammographic density (P < 0.001, fold change ≥1.5 with a low false discovery rate ( |
| doi_str_mv | 10.1007/s10549-009-0350-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_journals_366289167</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2054777411</sourcerecordid><originalsourceid>FETCH-proquest_journals_3662891673</originalsourceid><addsrcrecordid>eNqNj09LAzEQxYMouP75AN4G79HJrpt0z9Xam5ceBJGSdsfd1G6yZlJqv70RFDx6eDyY93swT4grhTcK0dyywvqukYhZVY0Sj0ShalNJUypzLApU2kg9QX0qzpg3mEGDTSEO97SOZJlaWDzOXlaU7Cuw67zdOt-B9S04_0tMn55LoM8xErMLPifQu66H6Pgd9mEgD3uX-j-NwQ5D6KIde7eG1fcxQUueXTpciJM3u2W6_PFzcT17WEzncozhY0eclpuwi_kPXlZal5MmL6j-BX0BlwFUSQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>366289167</pqid></control><display><type>article</type><title>Decreased TGF[beta] signaling and increased COX2 expression in high risk women with increased mammographic breast density</title><source>SpringerLink Journals - AutoHoldings</source><creator>Yang, Wei Tse ; Lewis, Michael T ; Hess, Kenneth ; Wong, Helen ; Tsimelzon, Anna ; Karadag, Nese ; Cairo, Michelina ; Wei, Caimaio ; Meric-bernstam, Funda ; Brown, Powel ; Arun, Banu ; Hortobagyi, Gabriel N ; Sahin, Aysegul ; Chang, Jenny C</creator><creatorcontrib>Yang, Wei Tse ; Lewis, Michael T ; Hess, Kenneth ; Wong, Helen ; Tsimelzon, Anna ; Karadag, Nese ; Cairo, Michelina ; Wei, Caimaio ; Meric-bernstam, Funda ; Brown, Powel ; Arun, Banu ; Hortobagyi, Gabriel N ; Sahin, Aysegul ; Chang, Jenny C</creatorcontrib><description>High mammographic density is associated with a increased risk of breast cancer. We hypothesized that specific pathways exist that are associated with increased mammographic density, and may therefore be used to identify potential targets for chemoprevention. Histologically confirmed normal breast tissue was collected from women undergoing breast surgery who had available demographic data and mammograms for review. Women with low versus high mammographic breast density were compared. Differentially expressed genes using Affymetrix HG U133Plus2 chips were identified in dense versus non-dense tissue. Immunohistochemical analysis (IHC) of estrogen receptor, progesterone receptor, Ki67, and COX2 expression was performed. About 66 women were identified, 28 (42%) had high, and 38 (58%) had low mammographic density. About 73 genes had differential expression between normal breast tissue with high and low mammographic density (P < 0.001, fold change ≥1.5 with a low false discovery rate (<10%). Network and canonical pathway analysis indicated decreased TGFβ signaling (TGFBR2, SOS, SMAD3, CD44 and TNFRSF11B) in dense breast tissue relative to non-dense breast. By IHC, only COX2 expression in the stroma was statistically significant on multivariate analysis. TGFβ ligands are currently the only growth factors known to prevent mammary epithelial cell proliferation. TGFβ signaling has been reported to be inhibited by COX-2, and these molecules are highly differentially expressed in individuals at high risk of developing breast cancer. These results strongly suggest that COX2 inhibition should be investigated for breast cancer prevention despite possible increase in cardiovascular risk. [PUBLICATION ABSTRACT]</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-009-0350-0</identifier><identifier>CODEN: BCTRD6</identifier><language>eng</language><publisher>Dordrecht: Springer Nature B.V</publisher><subject>Breast cancer ; Cancer research ; Density ; Gene expression ; Immunohistochemistry ; Mammography ; Preventive medicine ; Risk factors</subject><ispartof>Breast cancer research and treatment, 2010-01, Vol.119 (2), p.305</ispartof><rights>Springer Science+Business Media, LLC. 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids></links><search><creatorcontrib>Yang, Wei Tse</creatorcontrib><creatorcontrib>Lewis, Michael T</creatorcontrib><creatorcontrib>Hess, Kenneth</creatorcontrib><creatorcontrib>Wong, Helen</creatorcontrib><creatorcontrib>Tsimelzon, Anna</creatorcontrib><creatorcontrib>Karadag, Nese</creatorcontrib><creatorcontrib>Cairo, Michelina</creatorcontrib><creatorcontrib>Wei, Caimaio</creatorcontrib><creatorcontrib>Meric-bernstam, Funda</creatorcontrib><creatorcontrib>Brown, Powel</creatorcontrib><creatorcontrib>Arun, Banu</creatorcontrib><creatorcontrib>Hortobagyi, Gabriel N</creatorcontrib><creatorcontrib>Sahin, Aysegul</creatorcontrib><creatorcontrib>Chang, Jenny C</creatorcontrib><title>Decreased TGF[beta] signaling and increased COX2 expression in high risk women with increased mammographic breast density</title><title>Breast cancer research and treatment</title><description>High mammographic density is associated with a increased risk of breast cancer. We hypothesized that specific pathways exist that are associated with increased mammographic density, and may therefore be used to identify potential targets for chemoprevention. Histologically confirmed normal breast tissue was collected from women undergoing breast surgery who had available demographic data and mammograms for review. Women with low versus high mammographic breast density were compared. Differentially expressed genes using Affymetrix HG U133Plus2 chips were identified in dense versus non-dense tissue. Immunohistochemical analysis (IHC) of estrogen receptor, progesterone receptor, Ki67, and COX2 expression was performed. About 66 women were identified, 28 (42%) had high, and 38 (58%) had low mammographic density. About 73 genes had differential expression between normal breast tissue with high and low mammographic density (P < 0.001, fold change ≥1.5 with a low false discovery rate (<10%). Network and canonical pathway analysis indicated decreased TGFβ signaling (TGFBR2, SOS, SMAD3, CD44 and TNFRSF11B) in dense breast tissue relative to non-dense breast. By IHC, only COX2 expression in the stroma was statistically significant on multivariate analysis. TGFβ ligands are currently the only growth factors known to prevent mammary epithelial cell proliferation. TGFβ signaling has been reported to be inhibited by COX-2, and these molecules are highly differentially expressed in individuals at high risk of developing breast cancer. These results strongly suggest that COX2 inhibition should be investigated for breast cancer prevention despite possible increase in cardiovascular risk. [PUBLICATION ABSTRACT]</description><subject>Breast cancer</subject><subject>Cancer research</subject><subject>Density</subject><subject>Gene expression</subject><subject>Immunohistochemistry</subject><subject>Mammography</subject><subject>Preventive medicine</subject><subject>Risk factors</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNj09LAzEQxYMouP75AN4G79HJrpt0z9Xam5ceBJGSdsfd1G6yZlJqv70RFDx6eDyY93swT4grhTcK0dyywvqukYhZVY0Sj0ShalNJUypzLApU2kg9QX0qzpg3mEGDTSEO97SOZJlaWDzOXlaU7Cuw67zdOt-B9S04_0tMn55LoM8xErMLPifQu66H6Pgd9mEgD3uX-j-NwQ5D6KIde7eG1fcxQUueXTpciJM3u2W6_PFzcT17WEzncozhY0eclpuwi_kPXlZal5MmL6j-BX0BlwFUSQ</recordid><startdate>20100101</startdate><enddate>20100101</enddate><creator>Yang, Wei Tse</creator><creator>Lewis, Michael T</creator><creator>Hess, Kenneth</creator><creator>Wong, Helen</creator><creator>Tsimelzon, Anna</creator><creator>Karadag, Nese</creator><creator>Cairo, Michelina</creator><creator>Wei, Caimaio</creator><creator>Meric-bernstam, Funda</creator><creator>Brown, Powel</creator><creator>Arun, Banu</creator><creator>Hortobagyi, Gabriel N</creator><creator>Sahin, Aysegul</creator><creator>Chang, Jenny C</creator><general>Springer Nature B.V</general><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope></search><sort><creationdate>20100101</creationdate><title>Decreased TGF[beta] signaling and increased COX2 expression in high risk women with increased mammographic breast density</title><author>Yang, Wei Tse ; Lewis, Michael T ; Hess, Kenneth ; Wong, Helen ; Tsimelzon, Anna ; Karadag, Nese ; Cairo, Michelina ; Wei, Caimaio ; Meric-bernstam, Funda ; Brown, Powel ; Arun, Banu ; Hortobagyi, Gabriel N ; Sahin, Aysegul ; Chang, Jenny C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_journals_3662891673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Breast cancer</topic><topic>Cancer research</topic><topic>Density</topic><topic>Gene expression</topic><topic>Immunohistochemistry</topic><topic>Mammography</topic><topic>Preventive medicine</topic><topic>Risk factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Wei Tse</creatorcontrib><creatorcontrib>Lewis, Michael T</creatorcontrib><creatorcontrib>Hess, Kenneth</creatorcontrib><creatorcontrib>Wong, Helen</creatorcontrib><creatorcontrib>Tsimelzon, Anna</creatorcontrib><creatorcontrib>Karadag, Nese</creatorcontrib><creatorcontrib>Cairo, Michelina</creatorcontrib><creatorcontrib>Wei, Caimaio</creatorcontrib><creatorcontrib>Meric-bernstam, Funda</creatorcontrib><creatorcontrib>Brown, Powel</creatorcontrib><creatorcontrib>Arun, Banu</creatorcontrib><creatorcontrib>Hortobagyi, Gabriel N</creatorcontrib><creatorcontrib>Sahin, Aysegul</creatorcontrib><creatorcontrib>Chang, Jenny C</creatorcontrib><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</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>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</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><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Wei Tse</au><au>Lewis, Michael T</au><au>Hess, Kenneth</au><au>Wong, Helen</au><au>Tsimelzon, Anna</au><au>Karadag, Nese</au><au>Cairo, Michelina</au><au>Wei, Caimaio</au><au>Meric-bernstam, Funda</au><au>Brown, Powel</au><au>Arun, Banu</au><au>Hortobagyi, Gabriel N</au><au>Sahin, Aysegul</au><au>Chang, Jenny C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased TGF[beta] signaling and increased COX2 expression in high risk women with increased mammographic breast density</atitle><jtitle>Breast cancer research and treatment</jtitle><date>2010-01-01</date><risdate>2010</risdate><volume>119</volume><issue>2</issue><spage>305</spage><pages>305-</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><coden>BCTRD6</coden><abstract>High mammographic density is associated with a increased risk of breast cancer. We hypothesized that specific pathways exist that are associated with increased mammographic density, and may therefore be used to identify potential targets for chemoprevention. Histologically confirmed normal breast tissue was collected from women undergoing breast surgery who had available demographic data and mammograms for review. Women with low versus high mammographic breast density were compared. Differentially expressed genes using Affymetrix HG U133Plus2 chips were identified in dense versus non-dense tissue. Immunohistochemical analysis (IHC) of estrogen receptor, progesterone receptor, Ki67, and COX2 expression was performed. About 66 women were identified, 28 (42%) had high, and 38 (58%) had low mammographic density. About 73 genes had differential expression between normal breast tissue with high and low mammographic density (P < 0.001, fold change ≥1.5 with a low false discovery rate (<10%). Network and canonical pathway analysis indicated decreased TGFβ signaling (TGFBR2, SOS, SMAD3, CD44 and TNFRSF11B) in dense breast tissue relative to non-dense breast. By IHC, only COX2 expression in the stroma was statistically significant on multivariate analysis. TGFβ ligands are currently the only growth factors known to prevent mammary epithelial cell proliferation. TGFβ signaling has been reported to be inhibited by COX-2, and these molecules are highly differentially expressed in individuals at high risk of developing breast cancer. These results strongly suggest that COX2 inhibition should be investigated for breast cancer prevention despite possible increase in cardiovascular risk. [PUBLICATION ABSTRACT]</abstract><cop>Dordrecht</cop><pub>Springer Nature B.V</pub><doi>10.1007/s10549-009-0350-0</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-6806 |
| ispartof | Breast cancer research and treatment, 2010-01, Vol.119 (2), p.305 |
| issn | 0167-6806 1573-7217 |
| language | eng |
| recordid | cdi_proquest_journals_366289167 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | Breast cancer Cancer research Density Gene expression Immunohistochemistry Mammography Preventive medicine Risk factors |
| title | Decreased TGF[beta] signaling and increased COX2 expression in high risk women with increased mammographic breast density |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T09%3A35%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Decreased%20TGF%5Bbeta%5D%20signaling%20and%20increased%20COX2%20expression%20in%20high%20risk%20women%20with%20increased%20mammographic%20breast%20density&rft.jtitle=Breast%20cancer%20research%20and%20treatment&rft.au=Yang,%20Wei%20Tse&rft.date=2010-01-01&rft.volume=119&rft.issue=2&rft.spage=305&rft.pages=305-&rft.issn=0167-6806&rft.eissn=1573-7217&rft.coden=BCTRD6&rft_id=info:doi/10.1007/s10549-009-0350-0&rft_dat=%3Cproquest%3E2054777411%3C/proquest%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=366289167&rft_id=info:pmid/&rfr_iscdi=true |