Activated Protooncogenes in Human Lung Tumors from Smokers
Fourteen primary human lung tumor DNAs from smokers were analyzed for transforming activity by two DNA transfection assays. Activated protooncogenes were detected in 3 of 11 tumor DNAs by the NIII 3T3 focus assay, whereas activated protooncogenes were detected in 11 of 13 tumor DNAs by the NIH 3T3 c...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1991-02, Vol.88 (4), p.1085-1089 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Reynolds, Steven H. Anna, Colleen K. Brown, Kathryn C. Wiest, Jonathan S. Beattie, Edward J. Pero, Ronald W. Iglehart, J. Dirk Anderson, Marshall W. |
| description | Fourteen primary human lung tumor DNAs from smokers were analyzed for transforming activity by two DNA transfection assays. Activated protooncogenes were detected in 3 of 11 tumor DNAs by the NIII 3T3 focus assay, whereas activated protooncogenes were detected in 11 of 13 tumor DNAs by the NIH 3T3 cotransfection-nude mouse tumorigenicity assay. K- or NRAS genes activated by point mutation at codons 12 or 61 were detected in a large cell carcinoma, a squamous cell carcinoma, and 5 adenocarcinomas. An HRAS oncogene activated by a different mechanism was detected in an epidermoid carcinoma. One adenocarcinoma was found to contain an activated RAF gene. Two unidentified transforming genes were detected in a squamous cell carcinoma DNA and two adenocarcinoma DNAs. Eight of 10 lung adenocarcinomas that had formed metastases at the time of surgery were found to contain RAS oncogenes. No significant increase in metastasis was observed in the lung adenocarcinomas that contained one or more 6-kilobase EcoRI alleles of the LMYC gene. Overall, 12 of 14 (86%) of the lung tumor DNAs from smokers were found to contain activated protooncogenes. RAS oncogenes appear to play a role in the development of metastases in lung adenocarcinomas. |
| doi_str_mv | 10.1073/pnas.88.4.1085 |
| format | Article |
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Dirk ; Anderson, Marshall W.</creator><creatorcontrib>Reynolds, Steven H. ; Anna, Colleen K. ; Brown, Kathryn C. ; Wiest, Jonathan S. ; Beattie, Edward J. ; Pero, Ronald W. ; Iglehart, J. Dirk ; Anderson, Marshall W.</creatorcontrib><description>Fourteen primary human lung tumor DNAs from smokers were analyzed for transforming activity by two DNA transfection assays. Activated protooncogenes were detected in 3 of 11 tumor DNAs by the NIII 3T3 focus assay, whereas activated protooncogenes were detected in 11 of 13 tumor DNAs by the NIH 3T3 cotransfection-nude mouse tumorigenicity assay. K- or NRAS genes activated by point mutation at codons 12 or 61 were detected in a large cell carcinoma, a squamous cell carcinoma, and 5 adenocarcinomas. An HRAS oncogene activated by a different mechanism was detected in an epidermoid carcinoma. One adenocarcinoma was found to contain an activated RAF gene. Two unidentified transforming genes were detected in a squamous cell carcinoma DNA and two adenocarcinoma DNAs. Eight of 10 lung adenocarcinomas that had formed metastases at the time of surgery were found to contain RAS oncogenes. No significant increase in metastasis was observed in the lung adenocarcinomas that contained one or more 6-kilobase EcoRI alleles of the LMYC gene. Overall, 12 of 14 (86%) of the lung tumor DNAs from smokers were found to contain activated protooncogenes. RAS oncogenes appear to play a role in the development of metastases in lung adenocarcinomas.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.88.4.1085</identifier><identifier>PMID: 1996309</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>550200 - Biochemistry ; 560300 - Chemicals Metabolism & Toxicology ; Adenocarcinoma ; Adenocarcinoma - etiology ; Adenocarcinoma - genetics ; Adenocarcinoma - pathology ; AEROSOLS ; ANIMAL CELLS ; ANIMALS ; BASIC BIOLOGICAL SCIENCES ; BETA DECAY RADIOISOTOPES ; BETA-MINUS DECAY RADIOISOTOPES ; Biological and medical sciences ; BODY ; CARCINOGENESIS ; CARCINOMAS ; Cell Line ; Cell Transformation, Neoplastic ; CHEMICAL ACTIVATION ; Codons ; COLLOIDS ; DAYS LIVING RADIOISOTOPES ; DISEASES ; DISPERSIONS ; DNA ; DNA - genetics ; DNA POLYMERASES ; DNA, Neoplasm - genetics ; ENZYMES ; EPIDEMIOLOGY ; GENE AMPLIFICATION ; Gene Expression Regulation, Neoplastic ; GENES ; Humans ; ISOTOPES ; LIGHT NUCLEI ; Lung Neoplasms - etiology ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; LUNGS ; MAMMALS ; MAN ; Medical sciences ; METASTASES ; Metastasis ; Mice ; Mice, Nude ; Neoplasm Transplantation ; NEOPLASMS ; NIH 3T3 cells ; NUCLEI ; Nucleic Acid Hybridization ; NUCLEIC ACIDS ; NUCLEOTIDYLTRANSFERASES ; ODD-ODD NUCLEI ; ONCOGENES ; ORGANIC COMPOUNDS ; ORGANS ; PATHOGENESIS ; PHOSPHORUS 32 ; PHOSPHORUS ISOTOPES ; PHOSPHORUS-GROUP TRANSFERASES ; Polymerase Chain Reaction ; POLYMERASES ; PRIMATES ; PROTEINS ; Proto-Oncogenes ; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT ; RADIOISOTOPES ; RESIDUES ; RESPIRATORY SYSTEM ; RFLPS ; SMOKES ; Smoking - adverse effects ; SOLS ; Squamous cell carcinoma ; TOBACCO SMOKES ; Tobacco, tobacco smoking ; Toxicology ; Transfection ; TRANSFERASES ; Transplantation, Heterologous ; TUMOR CELLS ; Tumors ; VERTEBRATES</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1991-02, Vol.88 (4), p.1085-1089</ispartof><rights>Copyright 1991 The National Academy of Sciences of the United States of America</rights><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-7611d7c24e87d22fb24db62ca56024d4cd3ebc863c3de82ecaf8ef5e5cc74bbb3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/88/4.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2355938$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2355938$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,725,778,782,801,883,27907,27908,53774,53776,58000,58233</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19808508$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1996309$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/6161153$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Reynolds, Steven H.</creatorcontrib><creatorcontrib>Anna, Colleen K.</creatorcontrib><creatorcontrib>Brown, Kathryn C.</creatorcontrib><creatorcontrib>Wiest, Jonathan S.</creatorcontrib><creatorcontrib>Beattie, Edward J.</creatorcontrib><creatorcontrib>Pero, Ronald W.</creatorcontrib><creatorcontrib>Iglehart, J. Dirk</creatorcontrib><creatorcontrib>Anderson, Marshall W.</creatorcontrib><title>Activated Protooncogenes in Human Lung Tumors from Smokers</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Fourteen primary human lung tumor DNAs from smokers were analyzed for transforming activity by two DNA transfection assays. Activated protooncogenes were detected in 3 of 11 tumor DNAs by the NIII 3T3 focus assay, whereas activated protooncogenes were detected in 11 of 13 tumor DNAs by the NIH 3T3 cotransfection-nude mouse tumorigenicity assay. K- or NRAS genes activated by point mutation at codons 12 or 61 were detected in a large cell carcinoma, a squamous cell carcinoma, and 5 adenocarcinomas. An HRAS oncogene activated by a different mechanism was detected in an epidermoid carcinoma. One adenocarcinoma was found to contain an activated RAF gene. Two unidentified transforming genes were detected in a squamous cell carcinoma DNA and two adenocarcinoma DNAs. Eight of 10 lung adenocarcinomas that had formed metastases at the time of surgery were found to contain RAS oncogenes. No significant increase in metastasis was observed in the lung adenocarcinomas that contained one or more 6-kilobase EcoRI alleles of the LMYC gene. Overall, 12 of 14 (86%) of the lung tumor DNAs from smokers were found to contain activated protooncogenes. RAS oncogenes appear to play a role in the development of metastases in lung adenocarcinomas.</description><subject>550200 - Biochemistry</subject><subject>560300 - Chemicals Metabolism & Toxicology</subject><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - etiology</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - pathology</subject><subject>AEROSOLS</subject><subject>ANIMAL CELLS</subject><subject>ANIMALS</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>BETA DECAY RADIOISOTOPES</subject><subject>BETA-MINUS DECAY RADIOISOTOPES</subject><subject>Biological and medical sciences</subject><subject>BODY</subject><subject>CARCINOGENESIS</subject><subject>CARCINOMAS</subject><subject>Cell Line</subject><subject>Cell Transformation, Neoplastic</subject><subject>CHEMICAL ACTIVATION</subject><subject>Codons</subject><subject>COLLOIDS</subject><subject>DAYS LIVING RADIOISOTOPES</subject><subject>DISEASES</subject><subject>DISPERSIONS</subject><subject>DNA</subject><subject>DNA - genetics</subject><subject>DNA POLYMERASES</subject><subject>DNA, Neoplasm - genetics</subject><subject>ENZYMES</subject><subject>EPIDEMIOLOGY</subject><subject>GENE AMPLIFICATION</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>GENES</subject><subject>Humans</subject><subject>ISOTOPES</subject><subject>LIGHT NUCLEI</subject><subject>Lung Neoplasms - etiology</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>LUNGS</subject><subject>MAMMALS</subject><subject>MAN</subject><subject>Medical sciences</subject><subject>METASTASES</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neoplasm Transplantation</subject><subject>NEOPLASMS</subject><subject>NIH 3T3 cells</subject><subject>NUCLEI</subject><subject>Nucleic Acid Hybridization</subject><subject>NUCLEIC ACIDS</subject><subject>NUCLEOTIDYLTRANSFERASES</subject><subject>ODD-ODD NUCLEI</subject><subject>ONCOGENES</subject><subject>ORGANIC COMPOUNDS</subject><subject>ORGANS</subject><subject>PATHOGENESIS</subject><subject>PHOSPHORUS 32</subject><subject>PHOSPHORUS ISOTOPES</subject><subject>PHOSPHORUS-GROUP TRANSFERASES</subject><subject>Polymerase Chain Reaction</subject><subject>POLYMERASES</subject><subject>PRIMATES</subject><subject>PROTEINS</subject><subject>Proto-Oncogenes</subject><subject>RADIATION, THERMAL, AND OTHER ENVIRON. 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Dirk</creator><creator>Anderson, Marshall W.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</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>7X8</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>19910215</creationdate><title>Activated Protooncogenes in Human Lung Tumors from Smokers</title><author>Reynolds, Steven H. ; Anna, Colleen K. ; Brown, Kathryn C. ; Wiest, Jonathan S. ; Beattie, Edward J. ; Pero, Ronald W. ; Iglehart, J. Dirk ; Anderson, Marshall W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-7611d7c24e87d22fb24db62ca56024d4cd3ebc863c3de82ecaf8ef5e5cc74bbb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>550200 - Biochemistry</topic><topic>560300 - Chemicals Metabolism & Toxicology</topic><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - etiology</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - pathology</topic><topic>AEROSOLS</topic><topic>ANIMAL CELLS</topic><topic>ANIMALS</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>BETA DECAY RADIOISOTOPES</topic><topic>BETA-MINUS DECAY RADIOISOTOPES</topic><topic>Biological and medical sciences</topic><topic>BODY</topic><topic>CARCINOGENESIS</topic><topic>CARCINOMAS</topic><topic>Cell Line</topic><topic>Cell Transformation, Neoplastic</topic><topic>CHEMICAL ACTIVATION</topic><topic>Codons</topic><topic>COLLOIDS</topic><topic>DAYS LIVING RADIOISOTOPES</topic><topic>DISEASES</topic><topic>DISPERSIONS</topic><topic>DNA</topic><topic>DNA - genetics</topic><topic>DNA POLYMERASES</topic><topic>DNA, Neoplasm - genetics</topic><topic>ENZYMES</topic><topic>EPIDEMIOLOGY</topic><topic>GENE AMPLIFICATION</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>GENES</topic><topic>Humans</topic><topic>ISOTOPES</topic><topic>LIGHT NUCLEI</topic><topic>Lung Neoplasms - etiology</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>LUNGS</topic><topic>MAMMALS</topic><topic>MAN</topic><topic>Medical sciences</topic><topic>METASTASES</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Neoplasm Transplantation</topic><topic>NEOPLASMS</topic><topic>NIH 3T3 cells</topic><topic>NUCLEI</topic><topic>Nucleic Acid Hybridization</topic><topic>NUCLEIC ACIDS</topic><topic>NUCLEOTIDYLTRANSFERASES</topic><topic>ODD-ODD NUCLEI</topic><topic>ONCOGENES</topic><topic>ORGANIC COMPOUNDS</topic><topic>ORGANS</topic><topic>PATHOGENESIS</topic><topic>PHOSPHORUS 32</topic><topic>PHOSPHORUS ISOTOPES</topic><topic>PHOSPHORUS-GROUP TRANSFERASES</topic><topic>Polymerase Chain Reaction</topic><topic>POLYMERASES</topic><topic>PRIMATES</topic><topic>PROTEINS</topic><topic>Proto-Oncogenes</topic><topic>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</topic><topic>RADIOISOTOPES</topic><topic>RESIDUES</topic><topic>RESPIRATORY SYSTEM</topic><topic>RFLPS</topic><topic>SMOKES</topic><topic>Smoking - adverse effects</topic><topic>SOLS</topic><topic>Squamous cell carcinoma</topic><topic>TOBACCO SMOKES</topic><topic>Tobacco, tobacco smoking</topic><topic>Toxicology</topic><topic>Transfection</topic><topic>TRANSFERASES</topic><topic>Transplantation, Heterologous</topic><topic>TUMOR CELLS</topic><topic>Tumors</topic><topic>VERTEBRATES</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reynolds, Steven H.</creatorcontrib><creatorcontrib>Anna, Colleen K.</creatorcontrib><creatorcontrib>Brown, Kathryn C.</creatorcontrib><creatorcontrib>Wiest, Jonathan S.</creatorcontrib><creatorcontrib>Beattie, Edward J.</creatorcontrib><creatorcontrib>Pero, Ronald W.</creatorcontrib><creatorcontrib>Iglehart, J. Dirk</creatorcontrib><creatorcontrib>Anderson, Marshall W.</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>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reynolds, Steven H.</au><au>Anna, Colleen K.</au><au>Brown, Kathryn C.</au><au>Wiest, Jonathan S.</au><au>Beattie, Edward J.</au><au>Pero, Ronald W.</au><au>Iglehart, J. Dirk</au><au>Anderson, Marshall W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activated Protooncogenes in Human Lung Tumors from Smokers</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1991-02-15</date><risdate>1991</risdate><volume>88</volume><issue>4</issue><spage>1085</spage><epage>1089</epage><pages>1085-1089</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Fourteen primary human lung tumor DNAs from smokers were analyzed for transforming activity by two DNA transfection assays. Activated protooncogenes were detected in 3 of 11 tumor DNAs by the NIII 3T3 focus assay, whereas activated protooncogenes were detected in 11 of 13 tumor DNAs by the NIH 3T3 cotransfection-nude mouse tumorigenicity assay. K- or NRAS genes activated by point mutation at codons 12 or 61 were detected in a large cell carcinoma, a squamous cell carcinoma, and 5 adenocarcinomas. An HRAS oncogene activated by a different mechanism was detected in an epidermoid carcinoma. One adenocarcinoma was found to contain an activated RAF gene. Two unidentified transforming genes were detected in a squamous cell carcinoma DNA and two adenocarcinoma DNAs. Eight of 10 lung adenocarcinomas that had formed metastases at the time of surgery were found to contain RAS oncogenes. No significant increase in metastasis was observed in the lung adenocarcinomas that contained one or more 6-kilobase EcoRI alleles of the LMYC gene. Overall, 12 of 14 (86%) of the lung tumor DNAs from smokers were found to contain activated protooncogenes. RAS oncogenes appear to play a role in the development of metastases in lung adenocarcinomas.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>1996309</pmid><doi>10.1073/pnas.88.4.1085</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1991-02, Vol.88 (4), p.1085-1089 |
| issn | 0027-8424 1091-6490 |
| language | eng |
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| source | MEDLINE; Jstor Complete Legacy; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | 550200 - Biochemistry 560300 - Chemicals Metabolism & Toxicology Adenocarcinoma Adenocarcinoma - etiology Adenocarcinoma - genetics Adenocarcinoma - pathology AEROSOLS ANIMAL CELLS ANIMALS BASIC BIOLOGICAL SCIENCES BETA DECAY RADIOISOTOPES BETA-MINUS DECAY RADIOISOTOPES Biological and medical sciences BODY CARCINOGENESIS CARCINOMAS Cell Line Cell Transformation, Neoplastic CHEMICAL ACTIVATION Codons COLLOIDS DAYS LIVING RADIOISOTOPES DISEASES DISPERSIONS DNA DNA - genetics DNA POLYMERASES DNA, Neoplasm - genetics ENZYMES EPIDEMIOLOGY GENE AMPLIFICATION Gene Expression Regulation, Neoplastic GENES Humans ISOTOPES LIGHT NUCLEI Lung Neoplasms - etiology Lung Neoplasms - genetics Lung Neoplasms - pathology LUNGS MAMMALS MAN Medical sciences METASTASES Metastasis Mice Mice, Nude Neoplasm Transplantation NEOPLASMS NIH 3T3 cells NUCLEI Nucleic Acid Hybridization NUCLEIC ACIDS NUCLEOTIDYLTRANSFERASES ODD-ODD NUCLEI ONCOGENES ORGANIC COMPOUNDS ORGANS PATHOGENESIS PHOSPHORUS 32 PHOSPHORUS ISOTOPES PHOSPHORUS-GROUP TRANSFERASES Polymerase Chain Reaction POLYMERASES PRIMATES PROTEINS Proto-Oncogenes RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT RADIOISOTOPES RESIDUES RESPIRATORY SYSTEM RFLPS SMOKES Smoking - adverse effects SOLS Squamous cell carcinoma TOBACCO SMOKES Tobacco, tobacco smoking Toxicology Transfection TRANSFERASES Transplantation, Heterologous TUMOR CELLS Tumors VERTEBRATES |
| title | Activated Protooncogenes in Human Lung Tumors from Smokers |
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