FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer
Oestrogen receptor (ER)-positive breast cancer (BC) constitutes a heterogeneous group of tumours with regard to outcome and response to therapy. Accurate stratification of ER-positive BC according to risk of relapse and response to therapy will be achieved through an improved understanding of ER and...
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| creator | Habashy, Hany Onsy Rakha, Emad A. Aleskandarany, Mohammed Ahmed, Mohamed AH Green, Andrew R. Ellis, Ian O. Powe, Desmond G. |
| description | Oestrogen receptor (ER)-positive breast cancer (BC) constitutes a heterogeneous group of tumours with regard to outcome and response to therapy. Accurate stratification of ER-positive BC according to risk of relapse and response to therapy will be achieved through an improved understanding of ER and ER-related biological pathways. Recent studies have identified Forkhead box O3a (FOXO3a) transcription factor as an intracellular mediator of ERα expression and as an important downstream target of the Akt/PI3K pathway indicating a biological and potential clinical role for FOXO3a in ER-positive BC. In this study, we investigated the clinical relevance and biological associations of FOXO3a protein expression, using tissue microarrays and immunohistochemistry, in a large series of patients with invasive breast cancer. FOXO3a protein expression showed both nuclear and/or cytoplasmic staining patterns. FOXO3a predominant nuclear expression was positively associated with biomarkers of good prognosis including PgR, FOXA1 and p27 expression. There was an inverse association with mitotic counts, MIB1 growth fraction, C-MYC and PIK3CA expression. With respect to patient outcome, FOXO3a nuclear localisation was associated with longer BC specific survival (
P
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| doi_str_mv | 10.1007/s10549-010-1161-z |
| format | Article |
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P
< 0.001) and longer distant metastasis free interval (
P
= 0.001), independently of the well-established breast cancer prognostic factors. In conclusion, our results demonstrate the biological and prognostic role of FOXO3a protein expression and its subcellular localisation in ER-positive/luminal-like BC possibly through its involvement in controlling cell proliferation.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-010-1161-z</identifier><identifier>PMID: 21336599</identifier><identifier>CODEN: BCTRD6</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Adult ; Aged ; Antineoplastic Agents - therapeutic use ; Biological and medical sciences ; Biomarkers, Tumor - metabolism ; Breast cancer ; Breast Neoplasms - metabolism ; Breast Neoplasms - mortality ; Breast Neoplasms - pathology ; Cancer research ; Cancer therapies ; Cell Line, Tumor ; Cell Nucleus - metabolism ; Female ; Forkhead Box Protein O3 ; Forkhead Transcription Factors - metabolism ; Gynecology. Andrology. Obstetrics ; Humans ; Mammary gland diseases ; Medical prognosis ; Medical sciences ; Medicine ; Medicine & Public Health ; Middle Aged ; Neoplasm Staging ; Oncology ; Preclinical Study ; Prognosis ; Proteins ; Survival Analysis ; Treatment Outcome ; Tumors</subject><ispartof>Breast cancer research and treatment, 2011-08, Vol.129 (1), p.11-21</ispartof><rights>Springer Science+Business Media, LLC. 2011</rights><rights>2015 INIST-CNRS</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-f2fafbc781d12c13a5777f1f021868662c88ea317e772523cad50661c3b6b91d3</citedby><cites>FETCH-LOGICAL-c434t-f2fafbc781d12c13a5777f1f021868662c88ea317e772523cad50661c3b6b91d3</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/s10549-010-1161-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-010-1161-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24365086$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21336599$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00615379$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Habashy, Hany Onsy</creatorcontrib><creatorcontrib>Rakha, Emad A.</creatorcontrib><creatorcontrib>Aleskandarany, Mohammed</creatorcontrib><creatorcontrib>Ahmed, Mohamed AH</creatorcontrib><creatorcontrib>Green, Andrew R.</creatorcontrib><creatorcontrib>Ellis, Ian O.</creatorcontrib><creatorcontrib>Powe, Desmond G.</creatorcontrib><title>FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>Oestrogen receptor (ER)-positive breast cancer (BC) constitutes a heterogeneous group of tumours with regard to outcome and response to therapy. Accurate stratification of ER-positive BC according to risk of relapse and response to therapy will be achieved through an improved understanding of ER and ER-related biological pathways. Recent studies have identified Forkhead box O3a (FOXO3a) transcription factor as an intracellular mediator of ERα expression and as an important downstream target of the Akt/PI3K pathway indicating a biological and potential clinical role for FOXO3a in ER-positive BC. In this study, we investigated the clinical relevance and biological associations of FOXO3a protein expression, using tissue microarrays and immunohistochemistry, in a large series of patients with invasive breast cancer. FOXO3a protein expression showed both nuclear and/or cytoplasmic staining patterns. FOXO3a predominant nuclear expression was positively associated with biomarkers of good prognosis including PgR, FOXA1 and p27 expression. There was an inverse association with mitotic counts, MIB1 growth fraction, C-MYC and PIK3CA expression. With respect to patient outcome, FOXO3a nuclear localisation was associated with longer BC specific survival (
P
< 0.001) and longer distant metastasis free interval (
P
= 0.001), independently of the well-established breast cancer prognostic factors. In conclusion, our results demonstrate the biological and prognostic role of FOXO3a protein expression and its subcellular localisation in ER-positive/luminal-like BC possibly through its involvement in controlling cell proliferation.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Cell Line, Tumor</subject><subject>Cell Nucleus - metabolism</subject><subject>Female</subject><subject>Forkhead Box Protein O3</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Mammary gland diseases</subject><subject>Medical prognosis</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Preclinical Study</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kc9rFTEQx4Mo9ln9A7xIEEQ8rM4ku0n2WIq1woN3URA8hGw2-5qat6nJbsX-9WbZZwuCp2FmPvPzS8hLhPcIID9khKZuK0CoEAVWd4_IBhvJK8lQPiYbQCEroUCckGc5XwNAK6F9Sk4Yci6att2Q7xe7bztu6Djb4EyiIVoTfDaTjyP1mZqco_Vmcj395acruo-xpzcp7seYS9qPNMwHP5pQBf_D0S45kydqzWhdek6eDCZk9-JoT8nXi49fzi-r7e7T5_OzbWVrXk_VwAYzdFYq7JFZ5KaRUg44AEMllBDMKuUMR-mkZA3j1vQNCIGWd6Jrseen5N3a98oEfZP8waTfOhqvL8-2eokBCGy4bG-xsG9Xttzwc3Z50gefrQvBjC7OWSupmGybWhTy9T_kdZxTuXSBpOJteWyBcIVsijknN9zPR9CLRnrVSMPiF430Xal5dWw8dwfX31f8FaUAb46AyUWNIZVv-vzA1QUDtWzIVi6X1Lh36WHD_0__A-x7p_k</recordid><startdate>20110801</startdate><enddate>20110801</enddate><creator>Habashy, Hany Onsy</creator><creator>Rakha, Emad A.</creator><creator>Aleskandarany, Mohammed</creator><creator>Ahmed, Mohamed AH</creator><creator>Green, Andrew R.</creator><creator>Ellis, Ian O.</creator><creator>Powe, Desmond G.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><general>Springer Verlag</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><scope>1XC</scope><scope>VOOES</scope></search><sort><creationdate>20110801</creationdate><title>FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer</title><author>Habashy, Hany Onsy ; Rakha, Emad A. ; Aleskandarany, Mohammed ; Ahmed, Mohamed AH ; Green, Andrew R. ; Ellis, Ian O. ; Powe, Desmond G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-f2fafbc781d12c13a5777f1f021868662c88ea317e772523cad50661c3b6b91d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - mortality</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Cell Line, Tumor</topic><topic>Cell Nucleus - metabolism</topic><topic>Female</topic><topic>Forkhead Box Protein O3</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Gynecology. 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Accurate stratification of ER-positive BC according to risk of relapse and response to therapy will be achieved through an improved understanding of ER and ER-related biological pathways. Recent studies have identified Forkhead box O3a (FOXO3a) transcription factor as an intracellular mediator of ERα expression and as an important downstream target of the Akt/PI3K pathway indicating a biological and potential clinical role for FOXO3a in ER-positive BC. In this study, we investigated the clinical relevance and biological associations of FOXO3a protein expression, using tissue microarrays and immunohistochemistry, in a large series of patients with invasive breast cancer. FOXO3a protein expression showed both nuclear and/or cytoplasmic staining patterns. FOXO3a predominant nuclear expression was positively associated with biomarkers of good prognosis including PgR, FOXA1 and p27 expression. There was an inverse association with mitotic counts, MIB1 growth fraction, C-MYC and PIK3CA expression. With respect to patient outcome, FOXO3a nuclear localisation was associated with longer BC specific survival (
P
< 0.001) and longer distant metastasis free interval (
P
= 0.001), independently of the well-established breast cancer prognostic factors. In conclusion, our results demonstrate the biological and prognostic role of FOXO3a protein expression and its subcellular localisation in ER-positive/luminal-like BC possibly through its involvement in controlling cell proliferation.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>21336599</pmid><doi>10.1007/s10549-010-1161-z</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Antineoplastic Agents - therapeutic use Biological and medical sciences Biomarkers, Tumor - metabolism Breast cancer Breast Neoplasms - metabolism Breast Neoplasms - mortality Breast Neoplasms - pathology Cancer research Cancer therapies Cell Line, Tumor Cell Nucleus - metabolism Female Forkhead Box Protein O3 Forkhead Transcription Factors - metabolism Gynecology. Andrology. Obstetrics Humans Mammary gland diseases Medical prognosis Medical sciences Medicine Medicine & Public Health Middle Aged Neoplasm Staging Oncology Preclinical Study Prognosis Proteins Survival Analysis Treatment Outcome Tumors |
| title | FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer |
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