Activation of ras oncogenes and expression of tumor‐specific transplantation antigens in methylcholanthrene‐induced murine fibrosarcomas

The DNA of 22 fibrosarcomas, newly induced in BALB/c mice by subcutaneous doses of 3‐methylcholanthrene (3‐MCA), was tested in NIH 3T3 transformation assay. Activation of K‐ras and N‐ras was found in 7 and 3 cases respectively. No H‐ras activation was detected. Polymerase chain reaction and oligonuc...

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Veröffentlicht in:International journal of cancer 1991-02, Vol.47 (4), p.619-625
Hauptverfasser: Carbone, Giusi, Borrello, Maria Grazia, Molla, Alessandra, Rizzetti, Maria Grazia, Pierotti, Marco A., Porta, Giuseppe Della, Parmiani, Giorgio
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container_end_page 625
container_issue 4
container_start_page 619
container_title International journal of cancer
container_volume 47
creator Carbone, Giusi
Borrello, Maria Grazia
Molla, Alessandra
Rizzetti, Maria Grazia
Pierotti, Marco A.
Porta, Giuseppe Della
Parmiani, Giorgio
description The DNA of 22 fibrosarcomas, newly induced in BALB/c mice by subcutaneous doses of 3‐methylcholanthrene (3‐MCA), was tested in NIH 3T3 transformation assay. Activation of K‐ras and N‐ras was found in 7 and 3 cases respectively. No H‐ras activation was detected. Polymerase chain reaction and oligonucleotide hybridization performed on the DNA of the 22 sarcomas revealed 5 cases of K‐ras mutation at codon 12, 3 at codon 13 and I at both codons. One case of K13 mutation was not detectable by transfection. Three cases of mutation at codon 61 of N‐ras were also found, one of which was simultaneous with a K12 mutation. Tumor‐specific transplantation antigens (TSTA) were assessed in the 22 original tumors. Altogether 16 sarcomas were immunogenic, with the highest frequency of TSTA tumors (10/11 and 5/6) in the groups given 1.0 and 0.1 mg of 3‐MCA respectively, the lowest (1/5) in that with 0.01 mg of carcinogen; ras mutations occurred in the DNAs of 11 out of the 16 TSTA+ sarcomas, but none of the DNAs of the 6 TSTA‐ tumors showed ras mutation. The results suggest that 3‐MCA‐induced transformation of subcutaneous fibroblasts can involve mutations in codons 12, 13 or 61 of K‐ and N‐ but not H‐ras gene and that such mutation is accompanied by the expression of TSTA.
doi_str_mv 10.1002/ijc.2910470423
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Activation of K‐ras and N‐ras was found in 7 and 3 cases respectively. No H‐ras activation was detected. Polymerase chain reaction and oligonucleotide hybridization performed on the DNA of the 22 sarcomas revealed 5 cases of K‐ras mutation at codon 12, 3 at codon 13 and I at both codons. One case of K13 mutation was not detectable by transfection. Three cases of mutation at codon 61 of N‐ras were also found, one of which was simultaneous with a K12 mutation. Tumor‐specific transplantation antigens (TSTA) were assessed in the 22 original tumors. Altogether 16 sarcomas were immunogenic, with the highest frequency of TSTA tumors (10/11 and 5/6) in the groups given 1.0 and 0.1 mg of 3‐MCA respectively, the lowest (1/5) in that with 0.01 mg of carcinogen; ras mutations occurred in the DNAs of 11 out of the 16 TSTA+ sarcomas, but none of the DNAs of the 6 TSTA‐ tumors showed ras mutation. The results suggest that 3‐MCA‐induced transformation of subcutaneous fibroblasts can involve mutations in codons 12, 13 or 61 of K‐ and N‐ but not H‐ras gene and that such mutation is accompanied by the expression of TSTA.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.2910470423</identifier><identifier>PMID: 1995490</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>New York: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animal tumors. 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Activation of K‐ras and N‐ras was found in 7 and 3 cases respectively. No H‐ras activation was detected. Polymerase chain reaction and oligonucleotide hybridization performed on the DNA of the 22 sarcomas revealed 5 cases of K‐ras mutation at codon 12, 3 at codon 13 and I at both codons. One case of K13 mutation was not detectable by transfection. Three cases of mutation at codon 61 of N‐ras were also found, one of which was simultaneous with a K12 mutation. Tumor‐specific transplantation antigens (TSTA) were assessed in the 22 original tumors. Altogether 16 sarcomas were immunogenic, with the highest frequency of TSTA tumors (10/11 and 5/6) in the groups given 1.0 and 0.1 mg of 3‐MCA respectively, the lowest (1/5) in that with 0.01 mg of carcinogen; ras mutations occurred in the DNAs of 11 out of the 16 TSTA+ sarcomas, but none of the DNAs of the 6 TSTA‐ tumors showed ras mutation. The results suggest that 3‐MCA‐induced transformation of subcutaneous fibroblasts can involve mutations in codons 12, 13 or 61 of K‐ and N‐ but not H‐ras gene and that such mutation is accompanied by the expression of TSTA.</description><subject>Animal tumors. Experimental tumors</subject><subject>Animals</subject><subject>Antigens, Neoplasm - analysis</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Experimental tumors, general aspects</subject><subject>Female</subject><subject>Fibrosarcoma - chemically induced</subject><subject>Fibrosarcoma - genetics</subject><subject>Fibrosarcoma - immunology</subject><subject>Gene Expression Regulation</subject><subject>Genes, ras</subject><subject>Histocompatibility Antigens - analysis</subject><subject>Medical sciences</subject><subject>Methylcholanthrene</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Nucleic Acid Hybridization</subject><subject>Transfection</subject><subject>Tumors</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkD1v1DAYxy1EVY7CyobkBbYcfo3jsTpRKKrEUubIsZ9wrhI72Anltn4ABj4jnwSfclK7MfmR_i_-64fQG0q2lBD2wd_ZLdOUCEUE48_QhhKtKsKofI42xUAqRXn9Ar3M-Y4QSiUR5-icai2FJhv0-9LO_qeZfQw49jiZjGOw8TsEyNgEh-HXlCDnkz4vY0x_H_7kCazvvcVzMiFPgwnz2lEOX8IZ-4BHmPeHwe7jUd6nUlmSPrjFgsPjknwA3PsuxWySjaPJr9BZb4YMr0_vBfp29fF297m6-frpend5U1lBKK-YUoIzx6GRQtZQC21ZJztuoHBQijniNNEdd51jAIIK3RCle9WYjtWS1vwCvV97pxR_LJDndvTZwlB2QlxyS2VTM614MW5Xoy0jc4K-nZIfTTq0lLRH_G3B3z7iL4G3p-alG8E92lfeRX930k22ZugLPevzE1sjOaXHHr367v0Ah__82l5_2T3Z8A-_rqMy</recordid><startdate>19910220</startdate><enddate>19910220</enddate><creator>Carbone, Giusi</creator><creator>Borrello, Maria Grazia</creator><creator>Molla, Alessandra</creator><creator>Rizzetti, Maria Grazia</creator><creator>Pierotti, Marco A.</creator><creator>Porta, Giuseppe Della</creator><creator>Parmiani, Giorgio</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</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>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>19910220</creationdate><title>Activation of ras oncogenes and expression of tumor‐specific transplantation antigens in methylcholanthrene‐induced murine fibrosarcomas</title><author>Carbone, Giusi ; Borrello, Maria Grazia ; Molla, Alessandra ; Rizzetti, Maria Grazia ; Pierotti, Marco A. ; Porta, Giuseppe Della ; Parmiani, Giorgio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4013-277432d3e85456e649c2b5b3ae910772d0d909b3dbd2ee41498079f78ab265163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Animal tumors. Experimental tumors</topic><topic>Animals</topic><topic>Antigens, Neoplasm - analysis</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Experimental tumors, general aspects</topic><topic>Female</topic><topic>Fibrosarcoma - chemically induced</topic><topic>Fibrosarcoma - genetics</topic><topic>Fibrosarcoma - immunology</topic><topic>Gene Expression Regulation</topic><topic>Genes, ras</topic><topic>Histocompatibility Antigens - analysis</topic><topic>Medical sciences</topic><topic>Methylcholanthrene</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Nucleic Acid Hybridization</topic><topic>Transfection</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carbone, Giusi</creatorcontrib><creatorcontrib>Borrello, Maria Grazia</creatorcontrib><creatorcontrib>Molla, Alessandra</creatorcontrib><creatorcontrib>Rizzetti, Maria Grazia</creatorcontrib><creatorcontrib>Pierotti, Marco A.</creatorcontrib><creatorcontrib>Porta, Giuseppe Della</creatorcontrib><creatorcontrib>Parmiani, Giorgio</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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carbone, Giusi</au><au>Borrello, Maria Grazia</au><au>Molla, Alessandra</au><au>Rizzetti, Maria Grazia</au><au>Pierotti, Marco A.</au><au>Porta, Giuseppe Della</au><au>Parmiani, Giorgio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of ras oncogenes and expression of tumor‐specific transplantation antigens in methylcholanthrene‐induced murine fibrosarcomas</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>1991-02-20</date><risdate>1991</risdate><volume>47</volume><issue>4</issue><spage>619</spage><epage>625</epage><pages>619-625</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><abstract>The DNA of 22 fibrosarcomas, newly induced in BALB/c mice by subcutaneous doses of 3‐methylcholanthrene (3‐MCA), was tested in NIH 3T3 transformation assay. Activation of K‐ras and N‐ras was found in 7 and 3 cases respectively. No H‐ras activation was detected. Polymerase chain reaction and oligonucleotide hybridization performed on the DNA of the 22 sarcomas revealed 5 cases of K‐ras mutation at codon 12, 3 at codon 13 and I at both codons. One case of K13 mutation was not detectable by transfection. Three cases of mutation at codon 61 of N‐ras were also found, one of which was simultaneous with a K12 mutation. Tumor‐specific transplantation antigens (TSTA) were assessed in the 22 original tumors. Altogether 16 sarcomas were immunogenic, with the highest frequency of TSTA tumors (10/11 and 5/6) in the groups given 1.0 and 0.1 mg of 3‐MCA respectively, the lowest (1/5) in that with 0.01 mg of carcinogen; ras mutations occurred in the DNAs of 11 out of the 16 TSTA+ sarcomas, but none of the DNAs of the 6 TSTA‐ tumors showed ras mutation. The results suggest that 3‐MCA‐induced transformation of subcutaneous fibroblasts can involve mutations in codons 12, 13 or 61 of K‐ and N‐ but not H‐ras gene and that such mutation is accompanied by the expression of TSTA.</abstract><cop>New York</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>1995490</pmid><doi>10.1002/ijc.2910470423</doi><tpages>7</tpages></addata></record>
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subjects Animal tumors. Experimental tumors
Animals
Antigens, Neoplasm - analysis
Base Sequence
Biological and medical sciences
Experimental tumors, general aspects
Female
Fibrosarcoma - chemically induced
Fibrosarcoma - genetics
Fibrosarcoma - immunology
Gene Expression Regulation
Genes, ras
Histocompatibility Antigens - analysis
Medical sciences
Methylcholanthrene
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Mutation
Nucleic Acid Hybridization
Transfection
Tumors
title Activation of ras oncogenes and expression of tumor‐specific transplantation antigens in methylcholanthrene‐induced murine fibrosarcomas
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