BNIP3 Expression Is Linked with Hypoxia-Regulated Protein Expression and with Poor Prognosis in Non–Small Cell Lung Cancer
BNIP3 is a proapoptotic protein regulated by hypoxia-inducible factor 1. We analyzed BNIP3 expression in 105 tumor samples from early operable, non-small lung cancer and the relationship of expression to hypoxia-inducible factor 1α, other hypoxia-regulated pathways, and prognosis. There was strong c...
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| Veröffentlicht in: | Clinical cancer research 2004-08, Vol.10 (16), p.5566-5571 |
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| container_title | Clinical cancer research |
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| creator | GIATROMANOLAKI, Alexandra KOUKOURAKIS, Michael I SOWTER, Heidi M SIVRIDIS, Efthimios GIBSON, Spencer GATTER, Kevin C HARRIS, Adrian L |
| description | BNIP3 is a proapoptotic protein regulated by hypoxia-inducible factor 1. We analyzed BNIP3 expression in 105 tumor samples
from early operable, non-small lung cancer and the relationship of expression to hypoxia-inducible factor 1α, other hypoxia-regulated
pathways, and prognosis. There was strong cytoplasmic expression in >10% of cells in 40 of 105 cases. BNIP3 expression was
associated significantly with high hypoxia-inducible factor 1α ( P = 0.003), carbonic anhydrase 9 ( P = 0.04), and was inversely associated with bcl-2 expression ( P = 0.009). High BNIP3 expression was a major independent factor for overall survival. Thus, high expression of a hypoxia regulated
proapoptotic pathway was associated with a selection of an aggressive phenotype in vivo . |
| doi_str_mv | 10.1158/1078-0432.CCR-04-0076 |
| format | Article |
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from early operable, non-small lung cancer and the relationship of expression to hypoxia-inducible factor 1α, other hypoxia-regulated
pathways, and prognosis. There was strong cytoplasmic expression in >10% of cells in 40 of 105 cases. BNIP3 expression was
associated significantly with high hypoxia-inducible factor 1α ( P = 0.003), carbonic anhydrase 9 ( P = 0.04), and was inversely associated with bcl-2 expression ( P = 0.009). High BNIP3 expression was a major independent factor for overall survival. Thus, high expression of a hypoxia regulated
proapoptotic pathway was associated with a selection of an aggressive phenotype in vivo .</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-04-0076</identifier><identifier>PMID: 15328198</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adenocarcinoma - genetics ; Adenocarcinoma - pathology ; Antineoplastic agents ; Apoptosis ; Biological and medical sciences ; Carcinoma, Non-Small-Cell Lung - mortality ; Carcinoma, Non-Small-Cell Lung - pathology ; Cell Hypoxia ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; Immunohistochemistry ; Lung Neoplasms - mortality ; Lung Neoplasms - pathology ; Medical sciences ; Membrane Proteins - genetics ; Neoplasm Staging ; Neovascularization, Pathologic ; Pharmacology. Drug treatments ; Prognosis ; Proto-Oncogene Proteins - genetics ; RNA, Messenger - genetics ; Transcription Factors - genetics ; Tumors</subject><ispartof>Clinical cancer research, 2004-08, Vol.10 (16), p.5566-5571</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c566t-b3ad736f42fac3efd39d7c6adc3d8fc6613c78d7404c53bd3c69b18269b60ef43</citedby><cites>FETCH-LOGICAL-c566t-b3ad736f42fac3efd39d7c6adc3d8fc6613c78d7404c53bd3c69b18269b60ef43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,3343,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16057427$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15328198$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GIATROMANOLAKI, Alexandra</creatorcontrib><creatorcontrib>KOUKOURAKIS, Michael I</creatorcontrib><creatorcontrib>SOWTER, Heidi M</creatorcontrib><creatorcontrib>SIVRIDIS, Efthimios</creatorcontrib><creatorcontrib>GIBSON, Spencer</creatorcontrib><creatorcontrib>GATTER, Kevin C</creatorcontrib><creatorcontrib>HARRIS, Adrian L</creatorcontrib><title>BNIP3 Expression Is Linked with Hypoxia-Regulated Protein Expression and with Poor Prognosis in Non–Small Cell Lung Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>BNIP3 is a proapoptotic protein regulated by hypoxia-inducible factor 1. We analyzed BNIP3 expression in 105 tumor samples
from early operable, non-small lung cancer and the relationship of expression to hypoxia-inducible factor 1α, other hypoxia-regulated
pathways, and prognosis. There was strong cytoplasmic expression in >10% of cells in 40 of 105 cases. BNIP3 expression was
associated significantly with high hypoxia-inducible factor 1α ( P = 0.003), carbonic anhydrase 9 ( P = 0.04), and was inversely associated with bcl-2 expression ( P = 0.009). High BNIP3 expression was a major independent factor for overall survival. Thus, high expression of a hypoxia regulated
proapoptotic pathway was associated with a selection of an aggressive phenotype in vivo .</description><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - pathology</subject><subject>Antineoplastic agents</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Non-Small-Cell Lung - mortality</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Cell Hypoxia</subject><subject>Humans</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit</subject><subject>Immunohistochemistry</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - pathology</subject><subject>Medical sciences</subject><subject>Membrane Proteins - genetics</subject><subject>Neoplasm Staging</subject><subject>Neovascularization, Pathologic</subject><subject>Pharmacology. Drug treatments</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>Transcription Factors - genetics</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu1DAUQC0Eoi8-AZQNqF2kteNnlhD1MdKojAqsLY_tzBgy9mAnait1wT_wh3wJTieorGBzfWWd-9A9ALxG8BQhKs4Q5KKEBFenTXOTkxJCzp6BfUQpL3HF6POc_2H2wEFKXyFEBEHyEuwhiiuBarEPHj5czxa4OL_bRpuSC76YpWLu_DdrilvXr4ur-224c6q8sauhU33-XsTQW-f_rlF-ohchxBFY-ZBcKjJ1HfyvHz8_bVTXFY3NYT74VdEor208Ai9a1SX7anoPwZeL88_NVTn_eDlr3s9LTRnryyVWhmPWkqpVGtvW4NpwzZTR2IhWM4aw5sJwAommeGmwZvUSiSpHBm1L8CF4t-u7jeH7YFMvNy7pvIzyNgxJMiYQgZBl8PifIBKcCkJ5Xf23J-JM1JiJDNIdqGNIKdpWbqPbqHgvEZSjSjlqkqMmmVXmRI4qc92bacCw3FjzVDW5y8DbCVBJq66N-aYuPXEMUk4qnrmTHbd2q_Wti1bqx-tneVZFvX7cg0mab41_AykItk4</recordid><startdate>20040815</startdate><enddate>20040815</enddate><creator>GIATROMANOLAKI, Alexandra</creator><creator>KOUKOURAKIS, Michael I</creator><creator>SOWTER, Heidi M</creator><creator>SIVRIDIS, Efthimios</creator><creator>GIBSON, Spencer</creator><creator>GATTER, Kevin C</creator><creator>HARRIS, Adrian L</creator><general>American Association for Cancer Research</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>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20040815</creationdate><title>BNIP3 Expression Is Linked with Hypoxia-Regulated Protein Expression and with Poor Prognosis in Non–Small Cell Lung Cancer</title><author>GIATROMANOLAKI, Alexandra ; KOUKOURAKIS, Michael I ; SOWTER, Heidi M ; SIVRIDIS, Efthimios ; GIBSON, Spencer ; GATTER, Kevin C ; HARRIS, Adrian L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c566t-b3ad736f42fac3efd39d7c6adc3d8fc6613c78d7404c53bd3c69b18269b60ef43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - pathology</topic><topic>Antineoplastic agents</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Non-Small-Cell Lung - mortality</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Cell Hypoxia</topic><topic>Humans</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit</topic><topic>Immunohistochemistry</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - pathology</topic><topic>Medical sciences</topic><topic>Membrane Proteins - genetics</topic><topic>Neoplasm Staging</topic><topic>Neovascularization, Pathologic</topic><topic>Pharmacology. Drug treatments</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>Transcription Factors - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GIATROMANOLAKI, Alexandra</creatorcontrib><creatorcontrib>KOUKOURAKIS, Michael I</creatorcontrib><creatorcontrib>SOWTER, Heidi M</creatorcontrib><creatorcontrib>SIVRIDIS, Efthimios</creatorcontrib><creatorcontrib>GIBSON, Spencer</creatorcontrib><creatorcontrib>GATTER, Kevin C</creatorcontrib><creatorcontrib>HARRIS, Adrian L</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>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GIATROMANOLAKI, Alexandra</au><au>KOUKOURAKIS, Michael I</au><au>SOWTER, Heidi M</au><au>SIVRIDIS, Efthimios</au><au>GIBSON, Spencer</au><au>GATTER, Kevin C</au><au>HARRIS, Adrian L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BNIP3 Expression Is Linked with Hypoxia-Regulated Protein Expression and with Poor Prognosis in Non–Small Cell Lung Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2004-08-15</date><risdate>2004</risdate><volume>10</volume><issue>16</issue><spage>5566</spage><epage>5571</epage><pages>5566-5571</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>BNIP3 is a proapoptotic protein regulated by hypoxia-inducible factor 1. We analyzed BNIP3 expression in 105 tumor samples
from early operable, non-small lung cancer and the relationship of expression to hypoxia-inducible factor 1α, other hypoxia-regulated
pathways, and prognosis. There was strong cytoplasmic expression in >10% of cells in 40 of 105 cases. BNIP3 expression was
associated significantly with high hypoxia-inducible factor 1α ( P = 0.003), carbonic anhydrase 9 ( P = 0.04), and was inversely associated with bcl-2 expression ( P = 0.009). High BNIP3 expression was a major independent factor for overall survival. Thus, high expression of a hypoxia regulated
proapoptotic pathway was associated with a selection of an aggressive phenotype in vivo .</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>15328198</pmid><doi>10.1158/1078-0432.CCR-04-0076</doi><tpages>6</tpages></addata></record> |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adenocarcinoma - genetics Adenocarcinoma - pathology Antineoplastic agents Apoptosis Biological and medical sciences Carcinoma, Non-Small-Cell Lung - mortality Carcinoma, Non-Small-Cell Lung - pathology Cell Hypoxia Humans Hypoxia-Inducible Factor 1, alpha Subunit Immunohistochemistry Lung Neoplasms - mortality Lung Neoplasms - pathology Medical sciences Membrane Proteins - genetics Neoplasm Staging Neovascularization, Pathologic Pharmacology. Drug treatments Prognosis Proto-Oncogene Proteins - genetics RNA, Messenger - genetics Transcription Factors - genetics Tumors |
| title | BNIP3 Expression Is Linked with Hypoxia-Regulated Protein Expression and with Poor Prognosis in Non–Small Cell Lung Cancer |
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