An in vitro model of the early genetic events in multistage carcinogenesis of malignant insulinoma
The aim of this study was to establish an in vitro model to confirm earlier observations on the role of the myc/ras oncogenes as promoting factors in the process of normal Langerhans islet β cell transformation. For that purpose we infected primary mouse Langerhans islets with a recombinant retrovir...
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| Veröffentlicht in: | Carcinogenesis (New York) 1999-08, Vol.20 (8), p.1521-1528 |
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| creator | Katić, Maša Hadžija, Mirko Wrischer, Mercedes Pavelić, Krešimir |
| description | The aim of this study was to establish an in vitro model to confirm earlier observations on the role of the myc/ras oncogenes as promoting factors in the process of normal Langerhans islet β cell transformation. For that purpose we infected primary mouse Langerhans islets with a recombinant retrovirus containing the v-H-ras and v-myc oncogenes, before or after treatment with transforming growth factor α (TGFα). Normal Langerhans islets, when grown in culture, are viable for 2–3 weeks. After treatment with TGFα, viability was extended by 10 days, following which islets disintegrated. Langerhans islets transformed with v-H-ras and v-myc became immortal and insulin negative. Single infected β cells, liberated from a primary islet into the surrounding medium, gave rise to neo islet formation. Moreover, single infected β cells were able to grow and divide, even without fibroblast support. These results indicate that the myc and ras oncogenes are sufficient for commencement of β cell transformation and, therefore, could represent `early events' in the multistep carcinogenesis of insulinomas. |
| doi_str_mv | 10.1093/carcin/20.8.1521 |
| format | Article |
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For that purpose we infected primary mouse Langerhans islets with a recombinant retrovirus containing the v-H-ras and v-myc oncogenes, before or after treatment with transforming growth factor α (TGFα). Normal Langerhans islets, when grown in culture, are viable for 2–3 weeks. After treatment with TGFα, viability was extended by 10 days, following which islets disintegrated. Langerhans islets transformed with v-H-ras and v-myc became immortal and insulin negative. Single infected β cells, liberated from a primary islet into the surrounding medium, gave rise to neo islet formation. Moreover, single infected β cells were able to grow and divide, even without fibroblast support. These results indicate that the myc and ras oncogenes are sufficient for commencement of β cell transformation and, therefore, could represent `early events' in the multistep carcinogenesis of insulinomas.</description><identifier>ISSN: 0143-3334</identifier><identifier>ISSN: 1460-2180</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/20.8.1521</identifier><identifier>PMID: 10426801</identifier><identifier>CODEN: CRNGDP</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>3T3 Cells ; Animals ; Biological and medical sciences ; c.f.u ; Cell Transformation, Neoplastic - genetics ; colony forming units ; EGF-R ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; epidermal growth factor receptor ; FCS ; fetal calf serum ; Genes, myc - physiology ; Genes, ras - physiology ; Genetic Vectors - administration & dosage ; HeBS ; HEPES-buffered saline pH 7.05 ; insulinoma ; Insulinoma - genetics ; Islets of Langerhans ; Medical sciences ; Mice ; Mice, Inbred CBA ; myc gene ; Pancreatic Neoplasms - genetics ; PBS ; phosphate-buffered saline ; ras gene ; Retroviridae - drug effects ; TGFα ; Transfection ; transforming growth factor α ; Tumors. Hypoglycemia ; v-H-ras gene ; v-myc gene</subject><ispartof>Carcinogenesis (New York), 1999-08, Vol.20 (8), p.1521-1528</ispartof><rights>1999 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Aug 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-5da991d34f31bb9b7ea6c85df81c7e59b40023d54cf6ff44c37ec56590331493</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1917336$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10426801$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Katić, Maša</creatorcontrib><creatorcontrib>Hadžija, Mirko</creatorcontrib><creatorcontrib>Wrischer, Mercedes</creatorcontrib><creatorcontrib>Pavelić, Krešimir</creatorcontrib><title>An in vitro model of the early genetic events in multistage carcinogenesis of malignant insulinoma</title><title>Carcinogenesis (New York)</title><addtitle>Carcinogenesis</addtitle><description>The aim of this study was to establish an in vitro model to confirm earlier observations on the role of the myc/ras oncogenes as promoting factors in the process of normal Langerhans islet β cell transformation. For that purpose we infected primary mouse Langerhans islets with a recombinant retrovirus containing the v-H-ras and v-myc oncogenes, before or after treatment with transforming growth factor α (TGFα). Normal Langerhans islets, when grown in culture, are viable for 2–3 weeks. After treatment with TGFα, viability was extended by 10 days, following which islets disintegrated. Langerhans islets transformed with v-H-ras and v-myc became immortal and insulin negative. Single infected β cells, liberated from a primary islet into the surrounding medium, gave rise to neo islet formation. Moreover, single infected β cells were able to grow and divide, even without fibroblast support. These results indicate that the myc and ras oncogenes are sufficient for commencement of β cell transformation and, therefore, could represent `early events' in the multistep carcinogenesis of insulinomas.</description><subject>3T3 Cells</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>c.f.u</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>colony forming units</subject><subject>EGF-R</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>epidermal growth factor receptor</subject><subject>FCS</subject><subject>fetal calf serum</subject><subject>Genes, myc - physiology</subject><subject>Genes, ras - physiology</subject><subject>Genetic Vectors - administration & dosage</subject><subject>HeBS</subject><subject>HEPES-buffered saline pH 7.05</subject><subject>insulinoma</subject><subject>Insulinoma - genetics</subject><subject>Islets of Langerhans</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred CBA</subject><subject>myc gene</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>PBS</subject><subject>phosphate-buffered saline</subject><subject>ras gene</subject><subject>Retroviridae - drug effects</subject><subject>TGFα</subject><subject>Transfection</subject><subject>transforming growth factor α</subject><subject>Tumors. Hypoglycemia</subject><subject>v-H-ras gene</subject><subject>v-myc gene</subject><issn>0143-3334</issn><issn>1460-2180</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0T1v1TAUBmALgdrb0p0JRQh1y62Pj5PYY1vRFqkSQztULJbj2BcXxyl2UtF_T6JcAWJi8uDnvP54CXkHdAtU4pnRyfh4xuhWbKFi8IpsgNe0ZCDoa7KhwLFERH5IjnJ-pBRqrOQBOQTKWS0obEh7Hgsfi2c_pqHoh86GYnDF-M0WVqfwUuxstKM3hX22ccwL7acw-jzqnS3W44fFZJ-XwV4Hv4s6jrPMU5g3e_2WvHE6ZHuyX4_J_dWn-8ub8vbL9efL89vScIljWXVaSuiQO4S2lW1jdW1E1TkBprGVbDmlDLuKG1c7x7nBxpqqriRFhDnhmJyusU9p-DHZPKreZ2ND0NEOU1bQSKCC_Q9EFFywGX74Bz4OU4rzGxQDiUzWYkmjKzJpyDlZp56S73V6UUDVUpJaf0kxqoRaSppH3u9zp7a33V8Daysz-LgHOhsdXNLR-PzHyeWK9czKlc112J-_t3X6ruoGm0rdPHxV1wwvKLsDdYW_AKMNqgw</recordid><startdate>19990801</startdate><enddate>19990801</enddate><creator>Katić, Maša</creator><creator>Hadžija, Mirko</creator><creator>Wrischer, Mercedes</creator><creator>Pavelić, Krešimir</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><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>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>19990801</creationdate><title>An in vitro model of the early genetic events in multistage carcinogenesis of malignant insulinoma</title><author>Katić, Maša ; Hadžija, Mirko ; Wrischer, Mercedes ; Pavelić, Krešimir</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-5da991d34f31bb9b7ea6c85df81c7e59b40023d54cf6ff44c37ec56590331493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>3T3 Cells</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>c.f.u</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>colony forming units</topic><topic>EGF-R</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>epidermal growth factor receptor</topic><topic>FCS</topic><topic>fetal calf serum</topic><topic>Genes, myc - physiology</topic><topic>Genes, ras - physiology</topic><topic>Genetic Vectors - administration & dosage</topic><topic>HeBS</topic><topic>HEPES-buffered saline pH 7.05</topic><topic>insulinoma</topic><topic>Insulinoma - genetics</topic><topic>Islets of Langerhans</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred CBA</topic><topic>myc gene</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>PBS</topic><topic>phosphate-buffered saline</topic><topic>ras gene</topic><topic>Retroviridae - drug effects</topic><topic>TGFα</topic><topic>Transfection</topic><topic>transforming growth factor α</topic><topic>Tumors. Hypoglycemia</topic><topic>v-H-ras gene</topic><topic>v-myc gene</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Katić, Maša</creatorcontrib><creatorcontrib>Hadžija, Mirko</creatorcontrib><creatorcontrib>Wrischer, Mercedes</creatorcontrib><creatorcontrib>Pavelić, Krešimir</creatorcontrib><collection>Istex</collection><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>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Katić, Maša</au><au>Hadžija, Mirko</au><au>Wrischer, Mercedes</au><au>Pavelić, Krešimir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An in vitro model of the early genetic events in multistage carcinogenesis of malignant insulinoma</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>1999-08-01</date><risdate>1999</risdate><volume>20</volume><issue>8</issue><spage>1521</spage><epage>1528</epage><pages>1521-1528</pages><issn>0143-3334</issn><issn>1460-2180</issn><eissn>1460-2180</eissn><coden>CRNGDP</coden><abstract>The aim of this study was to establish an in vitro model to confirm earlier observations on the role of the myc/ras oncogenes as promoting factors in the process of normal Langerhans islet β cell transformation. For that purpose we infected primary mouse Langerhans islets with a recombinant retrovirus containing the v-H-ras and v-myc oncogenes, before or after treatment with transforming growth factor α (TGFα). Normal Langerhans islets, when grown in culture, are viable for 2–3 weeks. After treatment with TGFα, viability was extended by 10 days, following which islets disintegrated. Langerhans islets transformed with v-H-ras and v-myc became immortal and insulin negative. Single infected β cells, liberated from a primary islet into the surrounding medium, gave rise to neo islet formation. Moreover, single infected β cells were able to grow and divide, even without fibroblast support. These results indicate that the myc and ras oncogenes are sufficient for commencement of β cell transformation and, therefore, could represent `early events' in the multistep carcinogenesis of insulinomas.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>10426801</pmid><doi>10.1093/carcin/20.8.1521</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Carcinogenesis (New York), 1999-08, Vol.20 (8), p.1521-1528 |
| issn | 0143-3334 1460-2180 1460-2180 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | 3T3 Cells Animals Biological and medical sciences c.f.u Cell Transformation, Neoplastic - genetics colony forming units EGF-R Endocrine pancreas. Apud cells (diseases) Endocrinopathies epidermal growth factor receptor FCS fetal calf serum Genes, myc - physiology Genes, ras - physiology Genetic Vectors - administration & dosage HeBS HEPES-buffered saline pH 7.05 insulinoma Insulinoma - genetics Islets of Langerhans Medical sciences Mice Mice, Inbred CBA myc gene Pancreatic Neoplasms - genetics PBS phosphate-buffered saline ras gene Retroviridae - drug effects TGFα Transfection transforming growth factor α Tumors. Hypoglycemia v-H-ras gene v-myc gene |
| title | An in vitro model of the early genetic events in multistage carcinogenesis of malignant insulinoma |
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