Identification of a Mammary Transforming Gene (MAT1) Associated with Mouse Mammary Carcinogenesis
We have developed an efficient in vitro transformation system using N-methyl-N-nitrosourea that allows us to study the role of hormones and growth factors in mouse mammary tumorigenesis. Utilizing this system, we reported earlier that mammary tumors induced in vitro with N-methyl-N-nitrosourea in th...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1994-10, Vol.91 (21), p.9789-9793 |
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creator | Bera, Tapan Kumar Guzman, Raphael C. Miyamoto, Shigeki Panda, Dibyendu Kumar Sasaki, Masato Hanyu, Kazuhide Enami, Jumpei Nandi, Satyabrata |
description | We have developed an efficient in vitro transformation system using N-methyl-N-nitrosourea that allows us to study the role of hormones and growth factors in mouse mammary tumorigenesis. Utilizing this system, we reported earlier that mammary tumors induced in vitro with N-methyl-N-nitrosourea in the presence of mammogenic hormones (progesterone and prolactin) contain predominately an activated c-Ki-ras protooncogene with a G35 → A35 transitional mutation in the 12th codon. Mammary tumors induced in the presence of another mitogen, lithium (Li), do not have a mutation in the c-Ki-ras protooncogene. By using an expression cloning system, a plasmid clone containing a 1.75-kb cDNA insert has been isolated from this group of tumors. Nucleic acid sequence analysis of the insert reveals that it has a short open reading frame of 61 amino acids and that it does not have sequence homology with any known gene. The gene, designated MAT1, can neoplastically transform NIH 3T3 cells and also the mammary epithelial cell line TM3. Expression of this gene occurs in normal mouse tissues including mammary gland and is overexpressed in the original mammary tumors as indicated by Northern blot analysis. In vitro transcription and translation of the clone shows a protein product of 6000 Da, which agrees with the predicted open reading frame. |
doi_str_mv | 10.1073/pnas.91.21.9789 |
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Utilizing this system, we reported earlier that mammary tumors induced in vitro with N-methyl-N-nitrosourea in the presence of mammogenic hormones (progesterone and prolactin) contain predominately an activated c-Ki-ras protooncogene with a G35 → A35 transitional mutation in the 12th codon. Mammary tumors induced in the presence of another mitogen, lithium (Li), do not have a mutation in the c-Ki-ras protooncogene. By using an expression cloning system, a plasmid clone containing a 1.75-kb cDNA insert has been isolated from this group of tumors. Nucleic acid sequence analysis of the insert reveals that it has a short open reading frame of 61 amino acids and that it does not have sequence homology with any known gene. The gene, designated MAT1, can neoplastically transform NIH 3T3 cells and also the mammary epithelial cell line TM3. Expression of this gene occurs in normal mouse tissues including mammary gland and is overexpressed in the original mammary tumors as indicated by Northern blot analysis. In vitro transcription and translation of the clone shows a protein product of 6000 Da, which agrees with the predicted open reading frame.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.91.21.9789</identifier><identifier>PMID: 7937892</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>3T3 Cells ; Amino Acid Sequence ; Animals ; Base Sequence ; Brain - metabolism ; Carcinogens ; Cell Transformation, Neoplastic - genetics ; Complementary DNA ; DNA ; Epithelial cells ; Genes ; Genes, ras ; Hormones ; Humans ; Mammary Glands, Animal - drug effects ; Mammary Glands, Animal - pathology ; Mammary Neoplasms, Experimental - chemically induced ; Mammary Neoplasms, Experimental - genetics ; Mammary Neoplasms, Experimental - pathology ; Medical research ; Methylnitrosourea - toxicity ; Mice ; Mice, Inbred BALB C ; Mitogens ; Molecular Sequence Data ; Neoplasm Proteins - genetics ; Neoplasm Proteins - isolation & purification ; NIH 3T3 cells ; Oncogenes ; Point Mutation ; RNA ; Rodents ; Tumors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1994-10, Vol.91 (21), p.9789-9793</ispartof><rights>Copyright 1994 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Oct 11, 1994</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c520t-2be71a88bac899567538a75b11fd88f3f7e2381bef0e8164041f4713d8de2e5c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/91/21.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2365707$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2365707$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7937892$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bera, Tapan Kumar</creatorcontrib><creatorcontrib>Guzman, Raphael C.</creatorcontrib><creatorcontrib>Miyamoto, Shigeki</creatorcontrib><creatorcontrib>Panda, Dibyendu Kumar</creatorcontrib><creatorcontrib>Sasaki, Masato</creatorcontrib><creatorcontrib>Hanyu, Kazuhide</creatorcontrib><creatorcontrib>Enami, Jumpei</creatorcontrib><creatorcontrib>Nandi, Satyabrata</creatorcontrib><title>Identification of a Mammary Transforming Gene (MAT1) Associated with Mouse Mammary Carcinogenesis</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We have developed an efficient in vitro transformation system using N-methyl-N-nitrosourea that allows us to study the role of hormones and growth factors in mouse mammary tumorigenesis. Utilizing this system, we reported earlier that mammary tumors induced in vitro with N-methyl-N-nitrosourea in the presence of mammogenic hormones (progesterone and prolactin) contain predominately an activated c-Ki-ras protooncogene with a G35 → A35 transitional mutation in the 12th codon. Mammary tumors induced in the presence of another mitogen, lithium (Li), do not have a mutation in the c-Ki-ras protooncogene. By using an expression cloning system, a plasmid clone containing a 1.75-kb cDNA insert has been isolated from this group of tumors. Nucleic acid sequence analysis of the insert reveals that it has a short open reading frame of 61 amino acids and that it does not have sequence homology with any known gene. The gene, designated MAT1, can neoplastically transform NIH 3T3 cells and also the mammary epithelial cell line TM3. Expression of this gene occurs in normal mouse tissues including mammary gland and is overexpressed in the original mammary tumors as indicated by Northern blot analysis. In vitro transcription and translation of the clone shows a protein product of 6000 Da, which agrees with the predicted open reading frame.</description><subject>3T3 Cells</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Brain - metabolism</subject><subject>Carcinogens</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Complementary DNA</subject><subject>DNA</subject><subject>Epithelial cells</subject><subject>Genes</subject><subject>Genes, ras</subject><subject>Hormones</subject><subject>Humans</subject><subject>Mammary Glands, Animal - drug effects</subject><subject>Mammary Glands, Animal - pathology</subject><subject>Mammary Neoplasms, Experimental - chemically induced</subject><subject>Mammary Neoplasms, Experimental - genetics</subject><subject>Mammary Neoplasms, Experimental - pathology</subject><subject>Medical research</subject><subject>Methylnitrosourea - toxicity</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mitogens</subject><subject>Molecular Sequence Data</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - isolation & purification</subject><subject>NIH 3T3 cells</subject><subject>Oncogenes</subject><subject>Point Mutation</subject><subject>RNA</subject><subject>Rodents</subject><subject>Tumors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2P0zAYhC0EWsrCmQugiAMfh3T9OnFsS1yqCpaVtuJSzpbj2F1XiV3shI9_j6OWiuXAyYd55tWMB6HngJeAWXV18CotBSwJLAXj4gFaABZQNrXAD9ECY8JKXpP6MXqS0h5jLCjHF-iCiSrTZIHUTWf86KzTanTBF8EWqtioYVDxV7GNyicb4uD8rrg23hTvNqstvC9WKQXt1Gi64ocb74pNmJI529YqaufDLhuSS0_RI6v6ZJ6d3kv09dPH7fpzefvl-ma9ui01JXgsSWsYKM5bpbkQtGG04orRFsB2nNvKMkMqDq2x2HBoalyDrRlUHe8MMVRXl-jD8e5hagfT6Vwrql4eoptDyaCcvK94dyd34bus81-RbH9zssfwbTJplINL2vS98ia3k9BQAVxABl__A-7DFH2uJgkG0mDKqwxdHSEdQ0rR2HMOwHIeTs7DSQGSgJyHy46Xf8c_86elsv7qpM_GP-q9A2__C0g79f1ofo6ZfHEk92kM8YySqqEsR_sNRIS2gQ</recordid><startdate>19941011</startdate><enddate>19941011</enddate><creator>Bera, Tapan Kumar</creator><creator>Guzman, Raphael C.</creator><creator>Miyamoto, Shigeki</creator><creator>Panda, Dibyendu Kumar</creator><creator>Sasaki, Masato</creator><creator>Hanyu, Kazuhide</creator><creator>Enami, Jumpei</creator><creator>Nandi, Satyabrata</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>19941011</creationdate><title>Identification of a Mammary Transforming Gene (MAT1) Associated with Mouse Mammary Carcinogenesis</title><author>Bera, Tapan Kumar ; 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Utilizing this system, we reported earlier that mammary tumors induced in vitro with N-methyl-N-nitrosourea in the presence of mammogenic hormones (progesterone and prolactin) contain predominately an activated c-Ki-ras protooncogene with a G35 → A35 transitional mutation in the 12th codon. Mammary tumors induced in the presence of another mitogen, lithium (Li), do not have a mutation in the c-Ki-ras protooncogene. By using an expression cloning system, a plasmid clone containing a 1.75-kb cDNA insert has been isolated from this group of tumors. Nucleic acid sequence analysis of the insert reveals that it has a short open reading frame of 61 amino acids and that it does not have sequence homology with any known gene. The gene, designated MAT1, can neoplastically transform NIH 3T3 cells and also the mammary epithelial cell line TM3. Expression of this gene occurs in normal mouse tissues including mammary gland and is overexpressed in the original mammary tumors as indicated by Northern blot analysis. In vitro transcription and translation of the clone shows a protein product of 6000 Da, which agrees with the predicted open reading frame.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>7937892</pmid><doi>10.1073/pnas.91.21.9789</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 3T3 Cells Amino Acid Sequence Animals Base Sequence Brain - metabolism Carcinogens Cell Transformation, Neoplastic - genetics Complementary DNA DNA Epithelial cells Genes Genes, ras Hormones Humans Mammary Glands, Animal - drug effects Mammary Glands, Animal - pathology Mammary Neoplasms, Experimental - chemically induced Mammary Neoplasms, Experimental - genetics Mammary Neoplasms, Experimental - pathology Medical research Methylnitrosourea - toxicity Mice Mice, Inbred BALB C Mitogens Molecular Sequence Data Neoplasm Proteins - genetics Neoplasm Proteins - isolation & purification NIH 3T3 cells Oncogenes Point Mutation RNA Rodents Tumors |
title | Identification of a Mammary Transforming Gene (MAT1) Associated with Mouse Mammary Carcinogenesis |
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