Expression of Transforming Growth Factor Alpha and Epidermal Growth Factor Receptor in Rat Lung Neoplasms Induced by Plutonium-239
Ninety-two rat lung proliferative lesions and neoplasms induced by inhaled 239 PuO2 were evaluated for aberrant expression of transforming growth factor alpha (TGF-α) and epidermal growth factor receptor (EGFR). Expression of TGF-α protein, measured by immunohistochemistry, was higher in 94% of the...
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Veröffentlicht in: | Radiation Research 1994-11, Vol.140 (2), p.191-198 |
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description | Ninety-two rat lung proliferative lesions and neoplasms induced by inhaled 239 PuO2 were evaluated for aberrant expression of transforming growth factor alpha (TGF-α) and epidermal growth factor receptor (EGFR). Expression of TGF-α protein, measured by immunohistochemistry, was higher in 94% of the squamous cell carcinomas and 87% of the foci of alveolar epithelial squamous metaplasia than that exhibited by the normal-appearing, adjacent lung parenchyma. In contrast, only 20% of adenocarcinomas and foci of epithelial hyperplasia expressed elevated levels of TGF-α. Many neoplasms expressing TGF-α also expressed excessive levels of EGFR mRNA. Southern and DNA slot blot analyses showed that the elevated EGFR expression was not due to amplification of the EGFR gene. These data suggest that increased amounts of TGF-α were early alterations in the progression of plutonium-induced squamous cell carcinoma, and these increases may occur in parallel with overexpression of the receptor for this growth factor. Together, these alterations create a potential autocrine loop for sustaining clonal expansion of cells initiated by high-LET radiation. |
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Expression of TGF-α protein, measured by immunohistochemistry, was higher in 94% of the squamous cell carcinomas and 87% of the foci of alveolar epithelial squamous metaplasia than that exhibited by the normal-appearing, adjacent lung parenchyma. In contrast, only 20% of adenocarcinomas and foci of epithelial hyperplasia expressed elevated levels of TGF-α. Many neoplasms expressing TGF-α also expressed excessive levels of EGFR mRNA. Southern and DNA slot blot analyses showed that the elevated EGFR expression was not due to amplification of the EGFR gene. These data suggest that increased amounts of TGF-α were early alterations in the progression of plutonium-induced squamous cell carcinoma, and these increases may occur in parallel with overexpression of the receptor for this growth factor. Together, these alterations create a potential autocrine loop for sustaining clonal expansion of cells initiated by high-LET radiation.</description><identifier>ISSN: 0033-7587</identifier><identifier>EISSN: 1938-5404</identifier><identifier>DOI: 10.2307/3578903</identifier><identifier>PMID: 7938468</identifier><identifier>CODEN: RAREAE</identifier><language>eng</language><publisher>Oak Brook, Il: Radiation Research Society</publisher><subject>Adenocarcinoma ; Animals ; Biological and medical sciences ; BIOLOGICAL RADIATION EFFECTS ; BIOLOGY AND MEDICINE, APPLIED STUDIES ; BIOLOGY AND MEDICINE, BASIC STUDIES ; Carcinoma, Squamous Cell - etiology ; Carcinoma, Squamous Cell - metabolism ; Cell lines ; DNA ; ENZYME IMMUNOASSAY ; Female ; GENE AMPLIFICATION ; Growth factor receptors ; GROWTH FACTORS ; Immunohistochemistry ; Lesions ; LET ; Lung neoplasms ; Lung Neoplasms - etiology ; Lung Neoplasms - metabolism ; LUNGS ; Medical sciences ; Neoplasia ; NEOPLASMS ; Neoplasms, Radiation-Induced - metabolism ; Plutonium - toxicity ; PLUTONIUM 239 ; Pneumology ; Rats ; Rats, Inbred F344 ; Receptor, Epidermal Growth Factor - analysis ; Receptor, Epidermal Growth Factor - biosynthesis ; RNA ; Squamous cell carcinoma ; Transforming Growth Factor alpha - analysis ; Transforming Growth Factor alpha - biosynthesis ; Tumors of the respiratory system and mediastinum</subject><ispartof>Radiation Research, 1994-11, Vol.140 (2), p.191-198</ispartof><rights>Copyright 1994 The Radiation Research Society</rights><rights>1995 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c274t-a14ae2aded2e614e88e82e337e3a9393e261d55d3df9100cc39af08c33851d793</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3578903$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3578903$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3350723$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7938468$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/70205$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Stegelmeier, Bryan L.</creatorcontrib><creatorcontrib>Gillett, Nancy A.</creatorcontrib><creatorcontrib>Hahn, Fletcher F.</creatorcontrib><creatorcontrib>Rebar, Alan H.</creatorcontrib><creatorcontrib>Kelly, Gregory</creatorcontrib><title>Expression of Transforming Growth Factor Alpha and Epidermal Growth Factor Receptor in Rat Lung Neoplasms Induced by Plutonium-239</title><title>Radiation Research</title><addtitle>Radiat Res</addtitle><description>Ninety-two rat lung proliferative lesions and neoplasms induced by inhaled 239 PuO2 were evaluated for aberrant expression of transforming growth factor alpha (TGF-α) and epidermal growth factor receptor (EGFR). Expression of TGF-α protein, measured by immunohistochemistry, was higher in 94% of the squamous cell carcinomas and 87% of the foci of alveolar epithelial squamous metaplasia than that exhibited by the normal-appearing, adjacent lung parenchyma. In contrast, only 20% of adenocarcinomas and foci of epithelial hyperplasia expressed elevated levels of TGF-α. Many neoplasms expressing TGF-α also expressed excessive levels of EGFR mRNA. Southern and DNA slot blot analyses showed that the elevated EGFR expression was not due to amplification of the EGFR gene. These data suggest that increased amounts of TGF-α were early alterations in the progression of plutonium-induced squamous cell carcinoma, and these increases may occur in parallel with overexpression of the receptor for this growth factor. Together, these alterations create a potential autocrine loop for sustaining clonal expansion of cells initiated by high-LET radiation.</description><subject>Adenocarcinoma</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>BIOLOGICAL RADIATION EFFECTS</subject><subject>BIOLOGY AND MEDICINE, APPLIED STUDIES</subject><subject>BIOLOGY AND MEDICINE, BASIC STUDIES</subject><subject>Carcinoma, Squamous Cell - etiology</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Cell lines</subject><subject>DNA</subject><subject>ENZYME IMMUNOASSAY</subject><subject>Female</subject><subject>GENE AMPLIFICATION</subject><subject>Growth factor receptors</subject><subject>GROWTH FACTORS</subject><subject>Immunohistochemistry</subject><subject>Lesions</subject><subject>LET</subject><subject>Lung neoplasms</subject><subject>Lung Neoplasms - etiology</subject><subject>Lung Neoplasms - metabolism</subject><subject>LUNGS</subject><subject>Medical sciences</subject><subject>Neoplasia</subject><subject>NEOPLASMS</subject><subject>Neoplasms, Radiation-Induced - metabolism</subject><subject>Plutonium - toxicity</subject><subject>PLUTONIUM 239</subject><subject>Pneumology</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Receptor, Epidermal Growth Factor - analysis</subject><subject>Receptor, Epidermal Growth Factor - biosynthesis</subject><subject>RNA</subject><subject>Squamous cell carcinoma</subject><subject>Transforming Growth Factor alpha - analysis</subject><subject>Transforming Growth Factor alpha - biosynthesis</subject><subject>Tumors of the respiratory system and mediastinum</subject><issn>0033-7587</issn><issn>1938-5404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1r3DAQhkVo2W4-6C8I6FDIya2ksVfycQmbD1jaEpKz0UrjrhZbMpJNkmt-eRR2SSDQ08zwPswwDyHfOfspgMlfUElVMzgic16DKqqSlV_InDGAQlZKfiPHKe1YnvminpGZzFC5UHPysnoaIqbkgqehpfdR-9SG2Dv_j17H8Dhu6ZU2Y4h02Q1bTbW3dDU4i7HX3SfiDg0Ob43z9E6PdD3lJb8xDJ1OfaK33k4GLd0807_dNAbvpr4QUJ-Sr63uEp4d6gl5uFrdX94U6z_Xt5fLdWGELMdC81Kj0BatwAUvUSlUAgEkgq6hBhQLbqvKgm1rzpgxUOuWKQOgKm7zwyeE7veGNLomGTei2ZrgPZqxkUywKiMXe8TEkFLEthmi63V8bjhr3jw3B8-ZPN-Tw7Tp0b5zB7E5_3HIdTK6a7NX49I7BlAxKeAD26Us7r_XXgGqgo--</recordid><startdate>199411</startdate><enddate>199411</enddate><creator>Stegelmeier, Bryan L.</creator><creator>Gillett, Nancy A.</creator><creator>Hahn, Fletcher F.</creator><creator>Rebar, Alan H.</creator><creator>Kelly, Gregory</creator><general>Radiation Research Society</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>OTOTI</scope></search><sort><creationdate>199411</creationdate><title>Expression of Transforming Growth Factor Alpha and Epidermal Growth Factor Receptor in Rat Lung Neoplasms Induced by Plutonium-239</title><author>Stegelmeier, Bryan L. ; Gillett, Nancy A. ; Hahn, Fletcher F. ; Rebar, Alan H. ; Kelly, Gregory</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c274t-a14ae2aded2e614e88e82e337e3a9393e261d55d3df9100cc39af08c33851d793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Adenocarcinoma</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>BIOLOGICAL RADIATION EFFECTS</topic><topic>BIOLOGY AND MEDICINE, APPLIED STUDIES</topic><topic>BIOLOGY AND MEDICINE, BASIC STUDIES</topic><topic>Carcinoma, Squamous Cell - etiology</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Cell lines</topic><topic>DNA</topic><topic>ENZYME IMMUNOASSAY</topic><topic>Female</topic><topic>GENE AMPLIFICATION</topic><topic>Growth factor receptors</topic><topic>GROWTH FACTORS</topic><topic>Immunohistochemistry</topic><topic>Lesions</topic><topic>LET</topic><topic>Lung neoplasms</topic><topic>Lung Neoplasms - etiology</topic><topic>Lung Neoplasms - metabolism</topic><topic>LUNGS</topic><topic>Medical sciences</topic><topic>Neoplasia</topic><topic>NEOPLASMS</topic><topic>Neoplasms, Radiation-Induced - metabolism</topic><topic>Plutonium - toxicity</topic><topic>PLUTONIUM 239</topic><topic>Pneumology</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Receptor, Epidermal Growth Factor - analysis</topic><topic>Receptor, Epidermal Growth Factor - biosynthesis</topic><topic>RNA</topic><topic>Squamous cell carcinoma</topic><topic>Transforming Growth Factor alpha - analysis</topic><topic>Transforming Growth Factor alpha - biosynthesis</topic><topic>Tumors of the respiratory system and mediastinum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stegelmeier, Bryan L.</creatorcontrib><creatorcontrib>Gillett, Nancy A.</creatorcontrib><creatorcontrib>Hahn, Fletcher F.</creatorcontrib><creatorcontrib>Rebar, Alan H.</creatorcontrib><creatorcontrib>Kelly, Gregory</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>OSTI.GOV</collection><jtitle>Radiation Research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stegelmeier, Bryan L.</au><au>Gillett, Nancy A.</au><au>Hahn, Fletcher F.</au><au>Rebar, Alan H.</au><au>Kelly, Gregory</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of Transforming Growth Factor Alpha and Epidermal Growth Factor Receptor in Rat Lung Neoplasms Induced by Plutonium-239</atitle><jtitle>Radiation Research</jtitle><addtitle>Radiat Res</addtitle><date>1994-11</date><risdate>1994</risdate><volume>140</volume><issue>2</issue><spage>191</spage><epage>198</epage><pages>191-198</pages><issn>0033-7587</issn><eissn>1938-5404</eissn><coden>RAREAE</coden><abstract>Ninety-two rat lung proliferative lesions and neoplasms induced by inhaled 239 PuO2 were evaluated for aberrant expression of transforming growth factor alpha (TGF-α) and epidermal growth factor receptor (EGFR). Expression of TGF-α protein, measured by immunohistochemistry, was higher in 94% of the squamous cell carcinomas and 87% of the foci of alveolar epithelial squamous metaplasia than that exhibited by the normal-appearing, adjacent lung parenchyma. In contrast, only 20% of adenocarcinomas and foci of epithelial hyperplasia expressed elevated levels of TGF-α. Many neoplasms expressing TGF-α also expressed excessive levels of EGFR mRNA. Southern and DNA slot blot analyses showed that the elevated EGFR expression was not due to amplification of the EGFR gene. These data suggest that increased amounts of TGF-α were early alterations in the progression of plutonium-induced squamous cell carcinoma, and these increases may occur in parallel with overexpression of the receptor for this growth factor. Together, these alterations create a potential autocrine loop for sustaining clonal expansion of cells initiated by high-LET radiation.</abstract><cop>Oak Brook, Il</cop><pub>Radiation Research Society</pub><pmid>7938468</pmid><doi>10.2307/3578903</doi><tpages>8</tpages></addata></record> |
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subjects | Adenocarcinoma Animals Biological and medical sciences BIOLOGICAL RADIATION EFFECTS BIOLOGY AND MEDICINE, APPLIED STUDIES BIOLOGY AND MEDICINE, BASIC STUDIES Carcinoma, Squamous Cell - etiology Carcinoma, Squamous Cell - metabolism Cell lines DNA ENZYME IMMUNOASSAY Female GENE AMPLIFICATION Growth factor receptors GROWTH FACTORS Immunohistochemistry Lesions LET Lung neoplasms Lung Neoplasms - etiology Lung Neoplasms - metabolism LUNGS Medical sciences Neoplasia NEOPLASMS Neoplasms, Radiation-Induced - metabolism Plutonium - toxicity PLUTONIUM 239 Pneumology Rats Rats, Inbred F344 Receptor, Epidermal Growth Factor - analysis Receptor, Epidermal Growth Factor - biosynthesis RNA Squamous cell carcinoma Transforming Growth Factor alpha - analysis Transforming Growth Factor alpha - biosynthesis Tumors of the respiratory system and mediastinum |
title | Expression of Transforming Growth Factor Alpha and Epidermal Growth Factor Receptor in Rat Lung Neoplasms Induced by Plutonium-239 |
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