Distinct nuclear receptor expression in stroma adjacent to breast tumors
The interaction between breast tumor epithelial and stromal cells is vital for initial and recurrent tumor growth. While breast cancer-associated stromal cells provide a favorable environment for proliferation and metastasis, the molecular mechanisms contributing to this process are not fully unders...
Gespeichert in:
| Veröffentlicht in: | Breast cancer research and treatment 2013-11, Vol.142 (1), p.211-223 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 223 |
|---|---|
| container_issue | 1 |
| container_start_page | 211 |
| container_title | Breast cancer research and treatment |
| container_volume | 142 |
| creator | Knower, Kevin C. Chand, Ashwini L. Eriksson, Natalie Takagi, Kiyoshi Miki, Yasuhiro Sasano, Hironobu Visvader, Jane E. Lindeman, Geoffrey J. Funder, John W. Fuller, Peter J. Simpson, Evan R. Tilley, Wayne D. Leedman, Peter J. Graham, J. Dinny Muscat, George E. O. Clarke, Christine L. Clyne, Colin D. |
| description | The interaction between breast tumor epithelial and stromal cells is vital for initial and recurrent tumor growth. While breast cancer-associated stromal cells provide a favorable environment for proliferation and metastasis, the molecular mechanisms contributing to this process are not fully understood. Nuclear receptors (NRs) are intracellular transcription factors that directly regulate gene expression. Little is known about the status of NRs in cancer-associated stroma. Nuclear Receptor Low-Density Taqman Arrays were used to compare the gene expression profiles of all 48 NR family members in a collection of primary cultured cancer-associated fibroblasts (CAFs) obtained from estrogen receptor (ER)α positive breast cancers (
n
= 9) and normal breast adipose fibroblasts (NAFs) (
n
= 7). Thirty-three of 48 NRs were expressed in both the groups, while 11 NRs were not detected in either. Three NRs (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (
DAX-1
); estrogen-related receptor beta (
ERR-β
); and RAR-related orphan receptor beta (
ROR-β
)) were only detected in NAFs, while one NR (liver receptor homolog-1 (
LRH-1
)) was unique to CAFs. Of the NRs co-expressed, four were significantly down-regulated in CAFs compared with NAFs (RAR-related orphan receptor-α (
ROR
-α); Thyroid hormone receptor-β (
TR-β
); vitamin D receptor (
VDR
); and peroxisome proliferator-activated receptor-γ (
PPAR-γ
)). Quantitative immunohistochemistry for LRH-1, TR-β, and PPAR-γ proteins in stromal fibroblasts from an independent panel of breast cancers (ER-positive (
n
= 15), ER-negative (
n
= 15), normal (
n
= 14)) positively correlated with mRNA expression profiles. The differentially expressed NRs identified in tumor stroma are key mediators in aromatase regulation and subsequent estrogen production. Our findings reveal a distinct pattern of NR expression that therefore fits with a sustained and increased local estrogen microenvironment in ER-positive tumors. NRs in CAFs may provide a new avenue for the development of intratumoral-targeted therapies in breast cancer. |
| doi_str_mv | 10.1007/s10549-013-2716-6 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1490785191</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A352488789</galeid><sourcerecordid>A352488789</sourcerecordid><originalsourceid>FETCH-LOGICAL-c609t-1d0fce3a5f28910400695eb31a23cfe5ca7d1767e78a83bebe5b533a19cdb6a93</originalsourceid><addsrcrecordid>eNp1kU1v1DAQhiMEokvhB3BBkRCIS4rHjr-OVfkoUiUucLYcZ9J6ldiL7Ujl3-PVLrRFIB_G8jzvjGfepnkJ5AwIke8zEN7rjgDrqATRiUfNBrhknaQgHzcbAkJ2QhFx0jzLeUsI0ZLop80J7YFSpmHTXH7wufjgShtWN6NNbUKHuxJTi7e7hDn7GFof2lxSXGxrx611GEpbYjsktLne1iWm_Lx5Mtk544tjPG2-f_r47eKyu_r6-cvF-VXnBNGlg5FMDpnlE1UaSE-I0BwHBpYyNyF3Vo4ghUSprGIDDsgHzpgF7cZBWM1Om3eHursUf6yYi1l8djjPNmBcs4FeE6k4aKjo67_QbVxTqL-rVK80Fz3hd9S1ndH4MMWSrNsXNeeM014pqfZtz_5B1TPi4l0MOPn6_kDw9p7gBu1cbnKc11L3mR-CcABdijknnMwu-cWmnwaI2dtsDjabarPZ22xE1bw6TrYOC45_FL99rcCbI2Czs_OUbHA-33FS9wrofnh64HJNhWtM91b03-6_APK8vME</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1448956405</pqid></control><display><type>article</type><title>Distinct nuclear receptor expression in stroma adjacent to breast tumors</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Knower, Kevin C. ; Chand, Ashwini L. ; Eriksson, Natalie ; Takagi, Kiyoshi ; Miki, Yasuhiro ; Sasano, Hironobu ; Visvader, Jane E. ; Lindeman, Geoffrey J. ; Funder, John W. ; Fuller, Peter J. ; Simpson, Evan R. ; Tilley, Wayne D. ; Leedman, Peter J. ; Graham, J. Dinny ; Muscat, George E. O. ; Clarke, Christine L. ; Clyne, Colin D.</creator><creatorcontrib>Knower, Kevin C. ; Chand, Ashwini L. ; Eriksson, Natalie ; Takagi, Kiyoshi ; Miki, Yasuhiro ; Sasano, Hironobu ; Visvader, Jane E. ; Lindeman, Geoffrey J. ; Funder, John W. ; Fuller, Peter J. ; Simpson, Evan R. ; Tilley, Wayne D. ; Leedman, Peter J. ; Graham, J. Dinny ; Muscat, George E. O. ; Clarke, Christine L. ; Clyne, Colin D.</creatorcontrib><description>The interaction between breast tumor epithelial and stromal cells is vital for initial and recurrent tumor growth. While breast cancer-associated stromal cells provide a favorable environment for proliferation and metastasis, the molecular mechanisms contributing to this process are not fully understood. Nuclear receptors (NRs) are intracellular transcription factors that directly regulate gene expression. Little is known about the status of NRs in cancer-associated stroma. Nuclear Receptor Low-Density Taqman Arrays were used to compare the gene expression profiles of all 48 NR family members in a collection of primary cultured cancer-associated fibroblasts (CAFs) obtained from estrogen receptor (ER)α positive breast cancers (
n
= 9) and normal breast adipose fibroblasts (NAFs) (
n
= 7). Thirty-three of 48 NRs were expressed in both the groups, while 11 NRs were not detected in either. Three NRs (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (
DAX-1
); estrogen-related receptor beta (
ERR-β
); and RAR-related orphan receptor beta (
ROR-β
)) were only detected in NAFs, while one NR (liver receptor homolog-1 (
LRH-1
)) was unique to CAFs. Of the NRs co-expressed, four were significantly down-regulated in CAFs compared with NAFs (RAR-related orphan receptor-α (
ROR
-α); Thyroid hormone receptor-β (
TR-β
); vitamin D receptor (
VDR
); and peroxisome proliferator-activated receptor-γ (
PPAR-γ
)). Quantitative immunohistochemistry for LRH-1, TR-β, and PPAR-γ proteins in stromal fibroblasts from an independent panel of breast cancers (ER-positive (
n
= 15), ER-negative (
n
= 15), normal (
n
= 14)) positively correlated with mRNA expression profiles. The differentially expressed NRs identified in tumor stroma are key mediators in aromatase regulation and subsequent estrogen production. Our findings reveal a distinct pattern of NR expression that therefore fits with a sustained and increased local estrogen microenvironment in ER-positive tumors. NRs in CAFs may provide a new avenue for the development of intratumoral-targeted therapies in breast cancer.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-013-2716-6</identifier><identifier>PMID: 24122391</identifier><identifier>CODEN: BCTRD6</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Aged ; Aged, 80 and over ; Biological and medical sciences ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Brief Report ; Cancer research ; Cancer therapies ; Cellular biology ; Estrogen ; Female ; Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genetic transcription ; Gynecology. Andrology. Obstetrics ; Humans ; Immunohistochemistry ; Mammary gland diseases ; Medical sciences ; Medicine ; Medicine & Public Health ; Middle Aged ; Molecular biology ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Neoplasm Grading ; Oncology ; Proteins ; Receptor, ErbB-2 - metabolism ; Receptors, Cytoplasmic and Nuclear - genetics ; Receptors, Cytoplasmic and Nuclear - metabolism ; Receptors, Estrogen - metabolism ; Receptors, Progesterone - metabolism ; Risk Factors ; RNA ; Stromal Cells - metabolism ; Tumors</subject><ispartof>Breast cancer research and treatment, 2013-11, Vol.142 (1), p.211-223</ispartof><rights>Springer Science+Business Media New York 2013</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2013 Springer</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c609t-1d0fce3a5f28910400695eb31a23cfe5ca7d1767e78a83bebe5b533a19cdb6a93</citedby><cites>FETCH-LOGICAL-c609t-1d0fce3a5f28910400695eb31a23cfe5ca7d1767e78a83bebe5b533a19cdb6a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-013-2716-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-013-2716-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27948125$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24122391$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Knower, Kevin C.</creatorcontrib><creatorcontrib>Chand, Ashwini L.</creatorcontrib><creatorcontrib>Eriksson, Natalie</creatorcontrib><creatorcontrib>Takagi, Kiyoshi</creatorcontrib><creatorcontrib>Miki, Yasuhiro</creatorcontrib><creatorcontrib>Sasano, Hironobu</creatorcontrib><creatorcontrib>Visvader, Jane E.</creatorcontrib><creatorcontrib>Lindeman, Geoffrey J.</creatorcontrib><creatorcontrib>Funder, John W.</creatorcontrib><creatorcontrib>Fuller, Peter J.</creatorcontrib><creatorcontrib>Simpson, Evan R.</creatorcontrib><creatorcontrib>Tilley, Wayne D.</creatorcontrib><creatorcontrib>Leedman, Peter J.</creatorcontrib><creatorcontrib>Graham, J. Dinny</creatorcontrib><creatorcontrib>Muscat, George E. O.</creatorcontrib><creatorcontrib>Clarke, Christine L.</creatorcontrib><creatorcontrib>Clyne, Colin D.</creatorcontrib><title>Distinct nuclear receptor expression in stroma adjacent to breast tumors</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>The interaction between breast tumor epithelial and stromal cells is vital for initial and recurrent tumor growth. While breast cancer-associated stromal cells provide a favorable environment for proliferation and metastasis, the molecular mechanisms contributing to this process are not fully understood. Nuclear receptors (NRs) are intracellular transcription factors that directly regulate gene expression. Little is known about the status of NRs in cancer-associated stroma. Nuclear Receptor Low-Density Taqman Arrays were used to compare the gene expression profiles of all 48 NR family members in a collection of primary cultured cancer-associated fibroblasts (CAFs) obtained from estrogen receptor (ER)α positive breast cancers (
n
= 9) and normal breast adipose fibroblasts (NAFs) (
n
= 7). Thirty-three of 48 NRs were expressed in both the groups, while 11 NRs were not detected in either. Three NRs (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (
DAX-1
); estrogen-related receptor beta (
ERR-β
); and RAR-related orphan receptor beta (
ROR-β
)) were only detected in NAFs, while one NR (liver receptor homolog-1 (
LRH-1
)) was unique to CAFs. Of the NRs co-expressed, four were significantly down-regulated in CAFs compared with NAFs (RAR-related orphan receptor-α (
ROR
-α); Thyroid hormone receptor-β (
TR-β
); vitamin D receptor (
VDR
); and peroxisome proliferator-activated receptor-γ (
PPAR-γ
)). Quantitative immunohistochemistry for LRH-1, TR-β, and PPAR-γ proteins in stromal fibroblasts from an independent panel of breast cancers (ER-positive (
n
= 15), ER-negative (
n
= 15), normal (
n
= 14)) positively correlated with mRNA expression profiles. The differentially expressed NRs identified in tumor stroma are key mediators in aromatase regulation and subsequent estrogen production. Our findings reveal a distinct pattern of NR expression that therefore fits with a sustained and increased local estrogen microenvironment in ER-positive tumors. NRs in CAFs may provide a new avenue for the development of intratumoral-targeted therapies in breast cancer.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Brief Report</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Cellular biology</subject><subject>Estrogen</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic transcription</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Molecular biology</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Neoplasm Grading</subject><subject>Oncology</subject><subject>Proteins</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Receptors, Cytoplasmic and Nuclear - genetics</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Receptors, Progesterone - metabolism</subject><subject>Risk Factors</subject><subject>RNA</subject><subject>Stromal Cells - metabolism</subject><subject>Tumors</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><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>eNp1kU1v1DAQhiMEokvhB3BBkRCIS4rHjr-OVfkoUiUucLYcZ9J6ldiL7Ujl3-PVLrRFIB_G8jzvjGfepnkJ5AwIke8zEN7rjgDrqATRiUfNBrhknaQgHzcbAkJ2QhFx0jzLeUsI0ZLop80J7YFSpmHTXH7wufjgShtWN6NNbUKHuxJTi7e7hDn7GFof2lxSXGxrx611GEpbYjsktLne1iWm_Lx5Mtk544tjPG2-f_r47eKyu_r6-cvF-VXnBNGlg5FMDpnlE1UaSE-I0BwHBpYyNyF3Vo4ghUSprGIDDsgHzpgF7cZBWM1Om3eHursUf6yYi1l8djjPNmBcs4FeE6k4aKjo67_QbVxTqL-rVK80Fz3hd9S1ndH4MMWSrNsXNeeM014pqfZtz_5B1TPi4l0MOPn6_kDw9p7gBu1cbnKc11L3mR-CcABdijknnMwu-cWmnwaI2dtsDjabarPZ22xE1bw6TrYOC45_FL99rcCbI2Czs_OUbHA-33FS9wrofnh64HJNhWtM91b03-6_APK8vME</recordid><startdate>20131101</startdate><enddate>20131101</enddate><creator>Knower, Kevin C.</creator><creator>Chand, Ashwini L.</creator><creator>Eriksson, Natalie</creator><creator>Takagi, Kiyoshi</creator><creator>Miki, Yasuhiro</creator><creator>Sasano, Hironobu</creator><creator>Visvader, Jane E.</creator><creator>Lindeman, Geoffrey J.</creator><creator>Funder, John W.</creator><creator>Fuller, Peter J.</creator><creator>Simpson, Evan R.</creator><creator>Tilley, Wayne D.</creator><creator>Leedman, Peter J.</creator><creator>Graham, J. Dinny</creator><creator>Muscat, George E. O.</creator><creator>Clarke, Christine L.</creator><creator>Clyne, Colin D.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><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>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>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20131101</creationdate><title>Distinct nuclear receptor expression in stroma adjacent to breast tumors</title><author>Knower, Kevin C. ; Chand, Ashwini L. ; Eriksson, Natalie ; Takagi, Kiyoshi ; Miki, Yasuhiro ; Sasano, Hironobu ; Visvader, Jane E. ; Lindeman, Geoffrey J. ; Funder, John W. ; Fuller, Peter J. ; Simpson, Evan R. ; Tilley, Wayne D. ; Leedman, Peter J. ; Graham, J. Dinny ; Muscat, George E. O. ; Clarke, Christine L. ; Clyne, Colin D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c609t-1d0fce3a5f28910400695eb31a23cfe5ca7d1767e78a83bebe5b533a19cdb6a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Brief Report</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Cellular biology</topic><topic>Estrogen</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic transcription</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Molecular biology</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Neoplasm Grading</topic><topic>Oncology</topic><topic>Proteins</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Receptors, Cytoplasmic and Nuclear - genetics</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>Receptors, Estrogen - metabolism</topic><topic>Receptors, Progesterone - metabolism</topic><topic>Risk Factors</topic><topic>RNA</topic><topic>Stromal Cells - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Knower, Kevin C.</creatorcontrib><creatorcontrib>Chand, Ashwini L.</creatorcontrib><creatorcontrib>Eriksson, Natalie</creatorcontrib><creatorcontrib>Takagi, Kiyoshi</creatorcontrib><creatorcontrib>Miki, Yasuhiro</creatorcontrib><creatorcontrib>Sasano, Hironobu</creatorcontrib><creatorcontrib>Visvader, Jane E.</creatorcontrib><creatorcontrib>Lindeman, Geoffrey J.</creatorcontrib><creatorcontrib>Funder, John W.</creatorcontrib><creatorcontrib>Fuller, Peter J.</creatorcontrib><creatorcontrib>Simpson, Evan R.</creatorcontrib><creatorcontrib>Tilley, Wayne D.</creatorcontrib><creatorcontrib>Leedman, Peter J.</creatorcontrib><creatorcontrib>Graham, J. Dinny</creatorcontrib><creatorcontrib>Muscat, George E. O.</creatorcontrib><creatorcontrib>Clarke, Christine L.</creatorcontrib><creatorcontrib>Clyne, Colin D.</creatorcontrib><collection>Pascal-Francis</collection><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>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 Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Knower, Kevin C.</au><au>Chand, Ashwini L.</au><au>Eriksson, Natalie</au><au>Takagi, Kiyoshi</au><au>Miki, Yasuhiro</au><au>Sasano, Hironobu</au><au>Visvader, Jane E.</au><au>Lindeman, Geoffrey J.</au><au>Funder, John W.</au><au>Fuller, Peter J.</au><au>Simpson, Evan R.</au><au>Tilley, Wayne D.</au><au>Leedman, Peter J.</au><au>Graham, J. Dinny</au><au>Muscat, George E. O.</au><au>Clarke, Christine L.</au><au>Clyne, Colin D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distinct nuclear receptor expression in stroma adjacent to breast tumors</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2013-11-01</date><risdate>2013</risdate><volume>142</volume><issue>1</issue><spage>211</spage><epage>223</epage><pages>211-223</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><coden>BCTRD6</coden><abstract>The interaction between breast tumor epithelial and stromal cells is vital for initial and recurrent tumor growth. While breast cancer-associated stromal cells provide a favorable environment for proliferation and metastasis, the molecular mechanisms contributing to this process are not fully understood. Nuclear receptors (NRs) are intracellular transcription factors that directly regulate gene expression. Little is known about the status of NRs in cancer-associated stroma. Nuclear Receptor Low-Density Taqman Arrays were used to compare the gene expression profiles of all 48 NR family members in a collection of primary cultured cancer-associated fibroblasts (CAFs) obtained from estrogen receptor (ER)α positive breast cancers (
n
= 9) and normal breast adipose fibroblasts (NAFs) (
n
= 7). Thirty-three of 48 NRs were expressed in both the groups, while 11 NRs were not detected in either. Three NRs (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (
DAX-1
); estrogen-related receptor beta (
ERR-β
); and RAR-related orphan receptor beta (
ROR-β
)) were only detected in NAFs, while one NR (liver receptor homolog-1 (
LRH-1
)) was unique to CAFs. Of the NRs co-expressed, four were significantly down-regulated in CAFs compared with NAFs (RAR-related orphan receptor-α (
ROR
-α); Thyroid hormone receptor-β (
TR-β
); vitamin D receptor (
VDR
); and peroxisome proliferator-activated receptor-γ (
PPAR-γ
)). Quantitative immunohistochemistry for LRH-1, TR-β, and PPAR-γ proteins in stromal fibroblasts from an independent panel of breast cancers (ER-positive (
n
= 15), ER-negative (
n
= 15), normal (
n
= 14)) positively correlated with mRNA expression profiles. The differentially expressed NRs identified in tumor stroma are key mediators in aromatase regulation and subsequent estrogen production. Our findings reveal a distinct pattern of NR expression that therefore fits with a sustained and increased local estrogen microenvironment in ER-positive tumors. NRs in CAFs may provide a new avenue for the development of intratumoral-targeted therapies in breast cancer.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>24122391</pmid><doi>10.1007/s10549-013-2716-6</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-6806 |
| ispartof | Breast cancer research and treatment, 2013-11, Vol.142 (1), p.211-223 |
| issn | 0167-6806 1573-7217 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1490785191 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Aged Aged, 80 and over Biological and medical sciences Breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Brief Report Cancer research Cancer therapies Cellular biology Estrogen Female Gene Expression Gene Expression Profiling Gene Expression Regulation, Neoplastic Genetic transcription Gynecology. Andrology. Obstetrics Humans Immunohistochemistry Mammary gland diseases Medical sciences Medicine Medicine & Public Health Middle Aged Molecular biology Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neoplasm Grading Oncology Proteins Receptor, ErbB-2 - metabolism Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - metabolism Receptors, Estrogen - metabolism Receptors, Progesterone - metabolism Risk Factors RNA Stromal Cells - metabolism Tumors |
| title | Distinct nuclear receptor expression in stroma adjacent to breast tumors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T06%3A02%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Distinct%20nuclear%20receptor%20expression%20in%20stroma%20adjacent%20to%20breast%20tumors&rft.jtitle=Breast%20cancer%20research%20and%20treatment&rft.au=Knower,%20Kevin%20C.&rft.date=2013-11-01&rft.volume=142&rft.issue=1&rft.spage=211&rft.epage=223&rft.pages=211-223&rft.issn=0167-6806&rft.eissn=1573-7217&rft.coden=BCTRD6&rft_id=info:doi/10.1007/s10549-013-2716-6&rft_dat=%3Cgale_proqu%3EA352488789%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1448956405&rft_id=info:pmid/24122391&rft_galeid=A352488789&rfr_iscdi=true |