Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease
Cumulative exposure to estrogen (E) and progesterone (P) over the menstrual cycle significantly influences the risk of developing breast cancer. Despite the dogma that PR in the breast merely serves as a marker of an active estrogen receptor (ER), and as an inhibitor of the proliferative actions of...
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| Veröffentlicht in: | Oncotarget 2014-09, Vol.5 (18), p.8651-8664 |
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| creator | Hilton, Heidi N Doan, Tram B Graham, J Dinny Oakes, Samantha R Silvestri, Audrey Santucci, Nicole Kantimm, Silke Huschtscha, Lily I Ormandy, Christopher J Funder, John W Simpson, Evan R Kuczek, Elizabeth S Leedman, Peter J Tilley, Wayne D Fuller, Peter J Muscat, George E O Clarke, Christine L |
| description | Cumulative exposure to estrogen (E) and progesterone (P) over the menstrual cycle significantly influences the risk of developing breast cancer. Despite the dogma that PR in the breast merely serves as a marker of an active estrogen receptor (ER), and as an inhibitor of the proliferative actions of E, it is now clear that in the breast P increases proliferation independently of E action. We show here that the progesterone receptor (PR) and ER are expressed in different epithelial populations, and target non-overlapping pathways in the normal human breast. In breast cancer, PR becomes highly correlated with ER, and this convergence is associated with signaling pathways predictive of disease metastasis. These data challenge the established paradigm that ER and PR function co-operatively in normal breast, and have significant implications not only for our understanding of normal breast biology, but also for diagnosis, prognosis and/or treatment options in breast cancer patients. |
| doi_str_mv | 10.18632/oncotarget.2354 |
| format | Article |
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Despite the dogma that PR in the breast merely serves as a marker of an active estrogen receptor (ER), and as an inhibitor of the proliferative actions of E, it is now clear that in the breast P increases proliferation independently of E action. We show here that the progesterone receptor (PR) and ER are expressed in different epithelial populations, and target non-overlapping pathways in the normal human breast. In breast cancer, PR becomes highly correlated with ER, and this convergence is associated with signaling pathways predictive of disease metastasis. These data challenge the established paradigm that ER and PR function co-operatively in normal breast, and have significant implications not only for our understanding of normal breast biology, but also for diagnosis, prognosis and/or treatment options in breast cancer patients.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.2354</identifier><identifier>PMID: 25261374</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Animals ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - mortality ; Breast Neoplasms - pathology ; Carcinoma, Intraductal, Noninfiltrating - genetics ; Carcinoma, Intraductal, Noninfiltrating - metabolism ; Carcinoma, Intraductal, Noninfiltrating - mortality ; Carcinoma, Intraductal, Noninfiltrating - secondary ; Case-Control Studies ; Cell Lineage ; Cell Proliferation ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - metabolism ; Cell Transformation, Neoplastic - pathology ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Female ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Kaplan-Meier Estimate ; Mammary Glands, Animal - metabolism ; Mammary Glands, Human - metabolism ; Mammary Glands, Human - pathology ; Prognosis ; Receptor Cross-Talk ; Receptors, Estrogen - genetics ; Receptors, Estrogen - metabolism ; Receptors, Progesterone - genetics ; Receptors, Progesterone - metabolism ; Research Paper ; RNA, Messenger - metabolism ; Signal Transduction ; Time Factors</subject><ispartof>Oncotarget, 2014-09, Vol.5 (18), p.8651-8664</ispartof><rights>Copyright: © 2014 Hilton et al. 2014</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-af34e4666ab7d3ef57d8d619a0f3480c916c11bd32320ab286d6abfe6ae1ed443</citedby><cites>FETCH-LOGICAL-c396t-af34e4666ab7d3ef57d8d619a0f3480c916c11bd32320ab286d6abfe6ae1ed443</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226711/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226711/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25261374$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hilton, Heidi N</creatorcontrib><creatorcontrib>Doan, Tram B</creatorcontrib><creatorcontrib>Graham, J Dinny</creatorcontrib><creatorcontrib>Oakes, Samantha R</creatorcontrib><creatorcontrib>Silvestri, Audrey</creatorcontrib><creatorcontrib>Santucci, Nicole</creatorcontrib><creatorcontrib>Kantimm, Silke</creatorcontrib><creatorcontrib>Huschtscha, Lily I</creatorcontrib><creatorcontrib>Ormandy, Christopher J</creatorcontrib><creatorcontrib>Funder, John W</creatorcontrib><creatorcontrib>Simpson, Evan R</creatorcontrib><creatorcontrib>Kuczek, Elizabeth S</creatorcontrib><creatorcontrib>Leedman, Peter J</creatorcontrib><creatorcontrib>Tilley, Wayne D</creatorcontrib><creatorcontrib>Fuller, Peter J</creatorcontrib><creatorcontrib>Muscat, George E O</creatorcontrib><creatorcontrib>Clarke, Christine L</creatorcontrib><title>Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Cumulative exposure to estrogen (E) and progesterone (P) over the menstrual cycle significantly influences the risk of developing breast cancer. 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These data challenge the established paradigm that ER and PR function co-operatively in normal breast, and have significant implications not only for our understanding of normal breast biology, but also for diagnosis, prognosis and/or treatment options in breast cancer patients.</description><subject>Animals</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - pathology</subject><subject>Carcinoma, Intraductal, Noninfiltrating - genetics</subject><subject>Carcinoma, Intraductal, Noninfiltrating - metabolism</subject><subject>Carcinoma, Intraductal, Noninfiltrating - mortality</subject><subject>Carcinoma, Intraductal, Noninfiltrating - secondary</subject><subject>Case-Control Studies</subject><subject>Cell Lineage</subject><subject>Cell Proliferation</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Cell Transformation, Neoplastic - pathology</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Regulatory Networks</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Mammary Glands, Animal - metabolism</subject><subject>Mammary Glands, Human - metabolism</subject><subject>Mammary Glands, Human - pathology</subject><subject>Prognosis</subject><subject>Receptor Cross-Talk</subject><subject>Receptors, Estrogen - genetics</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Receptors, Progesterone - genetics</subject><subject>Receptors, Progesterone - metabolism</subject><subject>Research Paper</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction</subject><subject>Time Factors</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkctKxTAQhoMoKureleQFjjaXpq0LQcQbCIroukyT6THSJsckRzhv46OaejebZDL__w3DT8g-Kw5ZrQQ_8k77BGGO6ZCLUq6RbdbIZsbLUqz_eW-RvRifi3xKWdW82SRbvOSKiUpuk7dT_bK0AQ3V3r1ihjmN1Pf0yYfRO6TRzh0M1s2pdbQLCDFRDVkUjun5PQVn6N09TQFctMl6R_vgR9ovnZ4qGIYVNTYmm-uJ4DIWhm9Q8nSRZ1udfIjT1BFT_odk9eTKGtwlGz0MEfe-7h3yeHH-cHY1u7m9vD47vZlp0ag0g15IlEop6CojsC8rUxvFGihyoy50w5RmrDOCC15Ax2tlsrRHBcjQSCl2yMknd7HsRjQaXd5paBfBjhBWrQfb_u84-9TO_WsrOVcVYxlQfAJ08DEG7H-8rGg_Amt_A2unwLLl4O_MH8N3POIdZ2qaXA</recordid><startdate>20140930</startdate><enddate>20140930</enddate><creator>Hilton, Heidi N</creator><creator>Doan, Tram B</creator><creator>Graham, J Dinny</creator><creator>Oakes, Samantha R</creator><creator>Silvestri, Audrey</creator><creator>Santucci, Nicole</creator><creator>Kantimm, Silke</creator><creator>Huschtscha, Lily I</creator><creator>Ormandy, Christopher J</creator><creator>Funder, John W</creator><creator>Simpson, Evan R</creator><creator>Kuczek, Elizabeth S</creator><creator>Leedman, Peter J</creator><creator>Tilley, Wayne D</creator><creator>Fuller, Peter J</creator><creator>Muscat, George E O</creator><creator>Clarke, Christine L</creator><general>Impact Journals LLC</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>5PM</scope></search><sort><creationdate>20140930</creationdate><title>Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease</title><author>Hilton, Heidi N ; Doan, Tram B ; Graham, J Dinny ; Oakes, Samantha R ; Silvestri, Audrey ; Santucci, Nicole ; Kantimm, Silke ; Huschtscha, Lily I ; Ormandy, Christopher J ; Funder, John W ; Simpson, Evan R ; Kuczek, Elizabeth S ; Leedman, Peter J ; Tilley, Wayne D ; Fuller, Peter J ; Muscat, George E O ; Clarke, Christine L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-af34e4666ab7d3ef57d8d619a0f3480c916c11bd32320ab286d6abfe6ae1ed443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - mortality</topic><topic>Breast Neoplasms - pathology</topic><topic>Carcinoma, Intraductal, Noninfiltrating - genetics</topic><topic>Carcinoma, Intraductal, Noninfiltrating - metabolism</topic><topic>Carcinoma, Intraductal, Noninfiltrating - mortality</topic><topic>Carcinoma, Intraductal, Noninfiltrating - secondary</topic><topic>Case-Control Studies</topic><topic>Cell Lineage</topic><topic>Cell Proliferation</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Cell Transformation, Neoplastic - metabolism</topic><topic>Cell Transformation, Neoplastic - pathology</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - pathology</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Regulatory Networks</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Mammary Glands, Animal - metabolism</topic><topic>Mammary Glands, Human - metabolism</topic><topic>Mammary Glands, Human - pathology</topic><topic>Prognosis</topic><topic>Receptor Cross-Talk</topic><topic>Receptors, Estrogen - genetics</topic><topic>Receptors, Estrogen - metabolism</topic><topic>Receptors, Progesterone - genetics</topic><topic>Receptors, Progesterone - metabolism</topic><topic>Research Paper</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal Transduction</topic><topic>Time Factors</topic><toplevel>online_resources</toplevel><creatorcontrib>Hilton, Heidi N</creatorcontrib><creatorcontrib>Doan, Tram B</creatorcontrib><creatorcontrib>Graham, J Dinny</creatorcontrib><creatorcontrib>Oakes, Samantha R</creatorcontrib><creatorcontrib>Silvestri, Audrey</creatorcontrib><creatorcontrib>Santucci, Nicole</creatorcontrib><creatorcontrib>Kantimm, Silke</creatorcontrib><creatorcontrib>Huschtscha, Lily I</creatorcontrib><creatorcontrib>Ormandy, Christopher J</creatorcontrib><creatorcontrib>Funder, John W</creatorcontrib><creatorcontrib>Simpson, Evan R</creatorcontrib><creatorcontrib>Kuczek, Elizabeth S</creatorcontrib><creatorcontrib>Leedman, Peter J</creatorcontrib><creatorcontrib>Tilley, Wayne D</creatorcontrib><creatorcontrib>Fuller, Peter J</creatorcontrib><creatorcontrib>Muscat, George E O</creatorcontrib><creatorcontrib>Clarke, Christine L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hilton, Heidi N</au><au>Doan, Tram B</au><au>Graham, J Dinny</au><au>Oakes, Samantha R</au><au>Silvestri, Audrey</au><au>Santucci, Nicole</au><au>Kantimm, Silke</au><au>Huschtscha, Lily I</au><au>Ormandy, Christopher J</au><au>Funder, John W</au><au>Simpson, Evan R</au><au>Kuczek, Elizabeth S</au><au>Leedman, Peter J</au><au>Tilley, Wayne D</au><au>Fuller, Peter J</au><au>Muscat, George E O</au><au>Clarke, Christine L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2014-09-30</date><risdate>2014</risdate><volume>5</volume><issue>18</issue><spage>8651</spage><epage>8664</epage><pages>8651-8664</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Cumulative exposure to estrogen (E) and progesterone (P) over the menstrual cycle significantly influences the risk of developing breast cancer. Despite the dogma that PR in the breast merely serves as a marker of an active estrogen receptor (ER), and as an inhibitor of the proliferative actions of E, it is now clear that in the breast P increases proliferation independently of E action. We show here that the progesterone receptor (PR) and ER are expressed in different epithelial populations, and target non-overlapping pathways in the normal human breast. In breast cancer, PR becomes highly correlated with ER, and this convergence is associated with signaling pathways predictive of disease metastasis. 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| subjects | Animals Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - mortality Breast Neoplasms - pathology Carcinoma, Intraductal, Noninfiltrating - genetics Carcinoma, Intraductal, Noninfiltrating - metabolism Carcinoma, Intraductal, Noninfiltrating - mortality Carcinoma, Intraductal, Noninfiltrating - secondary Case-Control Studies Cell Lineage Cell Proliferation Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Cell Transformation, Neoplastic - pathology Epithelial Cells - metabolism Epithelial Cells - pathology Female Gene Expression Regulation, Neoplastic Gene Regulatory Networks Humans Kaplan-Meier Estimate Mammary Glands, Animal - metabolism Mammary Glands, Human - metabolism Mammary Glands, Human - pathology Prognosis Receptor Cross-Talk Receptors, Estrogen - genetics Receptors, Estrogen - metabolism Receptors, Progesterone - genetics Receptors, Progesterone - metabolism Research Paper RNA, Messenger - metabolism Signal Transduction Time Factors |
| title | Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease |
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