Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein
Backgroundl Aims: Chronic infection with hepatitis B virus is a high-risk factor for hepatocellular carcinoma in humans. The HBV X-protein, a multi-functional viral regulator, has been suspected to play a positive role in hepatocarcinogenesis, as demonstrated by the high incidence of hepatocellular...
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| Veröffentlicht in: | Journal of hepatology 1999-07, Vol.31 (1), p.123-132 |
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| creator | Yu, Dae-Yeul Moon, Hyung-Bae Son, Jin-Kyong Jeong, Sangkyun Yu, Seong-Lan Yoon, Heesik Han, Yong-Mahn Lee, Chul-Sang Park, Jung-Sun Lee, Chul-Ho Hyun, Byung-Hwa Murakami, Seishi Lee, Kyung-Kwang |
| description | Backgroundl Aims: Chronic infection with hepatitis B virus is a high-risk factor for hepatocellular carcinoma in humans. The HBV X-protein, a multi-functional viral regulator, has been suspected to play a positive role in hepatocarcinogenesis, as demonstrated by the high incidence of hepatocellular carcinoma in HBx-expressing transgenic mice, although it is still controversial. The aim of this study was to generate transgenic mice expressing the HBV X-gene under authentic promoter control and to test whether the gene products can cause hepatic tumors.
Methods: Three transgenic mouse lines were generated by microinjecting the X-gene construct into hybrid (C57BL/6×DBA) eggs. Gene expression was tested by protein and mRNA analyses. During an observation period of 18 months, mice were sacrificed and organs subjected to histologic examinations.
Results: Grossly defined hepatocellular carcinomas reproducibly were observed in mice expressing the X-protein, which were investigated through six generations from the age of 11 to 18 months. Among 14 transgenic mice investigated from the age of 11 to 18 months, 12 were found to have hepatocellular carcinoma, grossly or microscopically. The lesion of the hepatocellular carcinoma disclosed a significant increase in the proliferating cell nuclear antigen in the nuclei.
Conclusion: The incidence of hepatocellular carcinoma (86%) in our HBV X transgenic mice may be highly significant, since, except for one case, HBV X-gene transgenic mice produced in other laboratories did not develop liver tumor or any other pathologic phenomena. |
| doi_str_mv | 10.1016/S0168-8278(99)80172-X |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69927075</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S016882789980172X</els_id><sourcerecordid>69927075</sourcerecordid><originalsourceid>FETCH-LOGICAL-c508t-be584b59a3b8796f706aafdbea4f9777a59e48ec0688c3319a46f94ddf83de363</originalsourceid><addsrcrecordid>eNqFkU1v1DAQhi1ERbeFnwDyAaFyCNiJ449TBRXQSpU4ANLeLMcZt4MSZ7GTqvx7vM2KcuMyc3lez_gZQl5y9o4zLt9_K0VXulb6zJi3mnFVV9snZMMlYxWTgj8lm7_IMTnJ-SdjrGFGPCPHnIla1KbeEH8VPfYQPdAp0FvYuXnyMAzL4BL1LnmM0-goRjonF_MNRPR0xILD_S5Bzhhv6HwLaxRnzPQjvcO0ZLqtdmmaAeNzchTckOHFoZ-SH58_fb-4rK6_frm6-HBd-Zbpueqg1aJrjWs6rYwMiknnQt-BE8EopVxrQGjwTGrtm4YbJ2Qwou-DbnpoZHNK3qzvlrm_FsizHTHvP-MiTEu20phaMdUWsF1Bn6acEwS7Szi69NtyZvd27YNdu1dnjbEPdu225F4dBizdCP0_qVVnAV4fAJe9G0JR5jE_crrVivOCna8YFBt3CMlmj_sb9JjAz7af8D-b_AFEaph8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>69927075</pqid></control><display><type>article</type><title>Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Yu, Dae-Yeul ; Moon, Hyung-Bae ; Son, Jin-Kyong ; Jeong, Sangkyun ; Yu, Seong-Lan ; Yoon, Heesik ; Han, Yong-Mahn ; Lee, Chul-Sang ; Park, Jung-Sun ; Lee, Chul-Ho ; Hyun, Byung-Hwa ; Murakami, Seishi ; Lee, Kyung-Kwang</creator><creatorcontrib>Yu, Dae-Yeul ; Moon, Hyung-Bae ; Son, Jin-Kyong ; Jeong, Sangkyun ; Yu, Seong-Lan ; Yoon, Heesik ; Han, Yong-Mahn ; Lee, Chul-Sang ; Park, Jung-Sun ; Lee, Chul-Ho ; Hyun, Byung-Hwa ; Murakami, Seishi ; Lee, Kyung-Kwang</creatorcontrib><description>Backgroundl Aims: Chronic infection with hepatitis B virus is a high-risk factor for hepatocellular carcinoma in humans. The HBV X-protein, a multi-functional viral regulator, has been suspected to play a positive role in hepatocarcinogenesis, as demonstrated by the high incidence of hepatocellular carcinoma in HBx-expressing transgenic mice, although it is still controversial. The aim of this study was to generate transgenic mice expressing the HBV X-gene under authentic promoter control and to test whether the gene products can cause hepatic tumors.
Methods: Three transgenic mouse lines were generated by microinjecting the X-gene construct into hybrid (C57BL/6×DBA) eggs. Gene expression was tested by protein and mRNA analyses. During an observation period of 18 months, mice were sacrificed and organs subjected to histologic examinations.
Results: Grossly defined hepatocellular carcinomas reproducibly were observed in mice expressing the X-protein, which were investigated through six generations from the age of 11 to 18 months. Among 14 transgenic mice investigated from the age of 11 to 18 months, 12 were found to have hepatocellular carcinoma, grossly or microscopically. The lesion of the hepatocellular carcinoma disclosed a significant increase in the proliferating cell nuclear antigen in the nuclei.
Conclusion: The incidence of hepatocellular carcinoma (86%) in our HBV X transgenic mice may be highly significant, since, except for one case, HBV X-gene transgenic mice produced in other laboratories did not develop liver tumor or any other pathologic phenomena.</description><identifier>ISSN: 0168-8278</identifier><identifier>EISSN: 1600-0641</identifier><identifier>DOI: 10.1016/S0168-8278(99)80172-X</identifier><identifier>PMID: 10424292</identifier><identifier>CODEN: JOHEEC</identifier><language>eng</language><publisher>Oxford: Elsevier B.V</publisher><subject>Animals ; Biological and medical sciences ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - virology ; Enhancer Elements, Genetic ; Gastroenterology. Liver. Pancreas. Abdomen ; HBV X-gene ; Hepatic tumors ; Hepatitis B Antigens - genetics ; Hepatitis B virus - genetics ; Liver - metabolism ; Liver - pathology ; Liver - virology ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Liver Neoplasms - virology ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Mice ; Mice, Transgenic ; Proliferating cell nuclear antigen ; Promoter Regions, Genetic ; Restriction Mapping ; Reverse Transcriptase Polymerase Chain Reaction ; Trans-Activators - genetics ; Transcription, Genetic ; Transgenic mice ; Tumors</subject><ispartof>Journal of hepatology, 1999-07, Vol.31 (1), p.123-132</ispartof><rights>1999</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-be584b59a3b8796f706aafdbea4f9777a59e48ec0688c3319a46f94ddf83de363</citedby><cites>FETCH-LOGICAL-c508t-be584b59a3b8796f706aafdbea4f9777a59e48ec0688c3319a46f94ddf83de363</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0168-8278(99)80172-X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1858711$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10424292$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Dae-Yeul</creatorcontrib><creatorcontrib>Moon, Hyung-Bae</creatorcontrib><creatorcontrib>Son, Jin-Kyong</creatorcontrib><creatorcontrib>Jeong, Sangkyun</creatorcontrib><creatorcontrib>Yu, Seong-Lan</creatorcontrib><creatorcontrib>Yoon, Heesik</creatorcontrib><creatorcontrib>Han, Yong-Mahn</creatorcontrib><creatorcontrib>Lee, Chul-Sang</creatorcontrib><creatorcontrib>Park, Jung-Sun</creatorcontrib><creatorcontrib>Lee, Chul-Ho</creatorcontrib><creatorcontrib>Hyun, Byung-Hwa</creatorcontrib><creatorcontrib>Murakami, Seishi</creatorcontrib><creatorcontrib>Lee, Kyung-Kwang</creatorcontrib><title>Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein</title><title>Journal of hepatology</title><addtitle>J Hepatol</addtitle><description>Backgroundl Aims: Chronic infection with hepatitis B virus is a high-risk factor for hepatocellular carcinoma in humans. The HBV X-protein, a multi-functional viral regulator, has been suspected to play a positive role in hepatocarcinogenesis, as demonstrated by the high incidence of hepatocellular carcinoma in HBx-expressing transgenic mice, although it is still controversial. The aim of this study was to generate transgenic mice expressing the HBV X-gene under authentic promoter control and to test whether the gene products can cause hepatic tumors.
Methods: Three transgenic mouse lines were generated by microinjecting the X-gene construct into hybrid (C57BL/6×DBA) eggs. Gene expression was tested by protein and mRNA analyses. During an observation period of 18 months, mice were sacrificed and organs subjected to histologic examinations.
Results: Grossly defined hepatocellular carcinomas reproducibly were observed in mice expressing the X-protein, which were investigated through six generations from the age of 11 to 18 months. Among 14 transgenic mice investigated from the age of 11 to 18 months, 12 were found to have hepatocellular carcinoma, grossly or microscopically. The lesion of the hepatocellular carcinoma disclosed a significant increase in the proliferating cell nuclear antigen in the nuclei.
Conclusion: The incidence of hepatocellular carcinoma (86%) in our HBV X transgenic mice may be highly significant, since, except for one case, HBV X-gene transgenic mice produced in other laboratories did not develop liver tumor or any other pathologic phenomena.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - virology</subject><subject>Enhancer Elements, Genetic</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>HBV X-gene</subject><subject>Hepatic tumors</subject><subject>Hepatitis B Antigens - genetics</subject><subject>Hepatitis B virus - genetics</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver - virology</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - virology</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Proliferating cell nuclear antigen</subject><subject>Promoter Regions, Genetic</subject><subject>Restriction Mapping</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Trans-Activators - genetics</subject><subject>Transcription, Genetic</subject><subject>Transgenic mice</subject><subject>Tumors</subject><issn>0168-8278</issn><issn>1600-0641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi1ERbeFnwDyAaFyCNiJ449TBRXQSpU4ANLeLMcZt4MSZ7GTqvx7vM2KcuMyc3lez_gZQl5y9o4zLt9_K0VXulb6zJi3mnFVV9snZMMlYxWTgj8lm7_IMTnJ-SdjrGFGPCPHnIla1KbeEH8VPfYQPdAp0FvYuXnyMAzL4BL1LnmM0-goRjonF_MNRPR0xILD_S5Bzhhv6HwLaxRnzPQjvcO0ZLqtdmmaAeNzchTckOHFoZ-SH58_fb-4rK6_frm6-HBd-Zbpueqg1aJrjWs6rYwMiknnQt-BE8EopVxrQGjwTGrtm4YbJ2Qwou-DbnpoZHNK3qzvlrm_FsizHTHvP-MiTEu20phaMdUWsF1Bn6acEwS7Szi69NtyZvd27YNdu1dnjbEPdu225F4dBizdCP0_qVVnAV4fAJe9G0JR5jE_crrVivOCna8YFBt3CMlmj_sb9JjAz7af8D-b_AFEaph8</recordid><startdate>19990701</startdate><enddate>19990701</enddate><creator>Yu, Dae-Yeul</creator><creator>Moon, Hyung-Bae</creator><creator>Son, Jin-Kyong</creator><creator>Jeong, Sangkyun</creator><creator>Yu, Seong-Lan</creator><creator>Yoon, Heesik</creator><creator>Han, Yong-Mahn</creator><creator>Lee, Chul-Sang</creator><creator>Park, Jung-Sun</creator><creator>Lee, Chul-Ho</creator><creator>Hyun, Byung-Hwa</creator><creator>Murakami, Seishi</creator><creator>Lee, Kyung-Kwang</creator><general>Elsevier B.V</general><general>Elsevier</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></search><sort><creationdate>19990701</creationdate><title>Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein</title><author>Yu, Dae-Yeul ; Moon, Hyung-Bae ; Son, Jin-Kyong ; Jeong, Sangkyun ; Yu, Seong-Lan ; Yoon, Heesik ; Han, Yong-Mahn ; Lee, Chul-Sang ; Park, Jung-Sun ; Lee, Chul-Ho ; Hyun, Byung-Hwa ; Murakami, Seishi ; Lee, Kyung-Kwang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c508t-be584b59a3b8796f706aafdbea4f9777a59e48ec0688c3319a46f94ddf83de363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - virology</topic><topic>Enhancer Elements, Genetic</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>HBV X-gene</topic><topic>Hepatic tumors</topic><topic>Hepatitis B Antigens - genetics</topic><topic>Hepatitis B virus - genetics</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver - virology</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - virology</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Proliferating cell nuclear antigen</topic><topic>Promoter Regions, Genetic</topic><topic>Restriction Mapping</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Trans-Activators - genetics</topic><topic>Transcription, Genetic</topic><topic>Transgenic mice</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Dae-Yeul</creatorcontrib><creatorcontrib>Moon, Hyung-Bae</creatorcontrib><creatorcontrib>Son, Jin-Kyong</creatorcontrib><creatorcontrib>Jeong, Sangkyun</creatorcontrib><creatorcontrib>Yu, Seong-Lan</creatorcontrib><creatorcontrib>Yoon, Heesik</creatorcontrib><creatorcontrib>Han, Yong-Mahn</creatorcontrib><creatorcontrib>Lee, Chul-Sang</creatorcontrib><creatorcontrib>Park, Jung-Sun</creatorcontrib><creatorcontrib>Lee, Chul-Ho</creatorcontrib><creatorcontrib>Hyun, Byung-Hwa</creatorcontrib><creatorcontrib>Murakami, Seishi</creatorcontrib><creatorcontrib>Lee, Kyung-Kwang</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><jtitle>Journal of hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Dae-Yeul</au><au>Moon, Hyung-Bae</au><au>Son, Jin-Kyong</au><au>Jeong, Sangkyun</au><au>Yu, Seong-Lan</au><au>Yoon, Heesik</au><au>Han, Yong-Mahn</au><au>Lee, Chul-Sang</au><au>Park, Jung-Sun</au><au>Lee, Chul-Ho</au><au>Hyun, Byung-Hwa</au><au>Murakami, Seishi</au><au>Lee, Kyung-Kwang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein</atitle><jtitle>Journal of hepatology</jtitle><addtitle>J Hepatol</addtitle><date>1999-07-01</date><risdate>1999</risdate><volume>31</volume><issue>1</issue><spage>123</spage><epage>132</epage><pages>123-132</pages><issn>0168-8278</issn><eissn>1600-0641</eissn><coden>JOHEEC</coden><abstract>Backgroundl Aims: Chronic infection with hepatitis B virus is a high-risk factor for hepatocellular carcinoma in humans. The HBV X-protein, a multi-functional viral regulator, has been suspected to play a positive role in hepatocarcinogenesis, as demonstrated by the high incidence of hepatocellular carcinoma in HBx-expressing transgenic mice, although it is still controversial. The aim of this study was to generate transgenic mice expressing the HBV X-gene under authentic promoter control and to test whether the gene products can cause hepatic tumors.
Methods: Three transgenic mouse lines were generated by microinjecting the X-gene construct into hybrid (C57BL/6×DBA) eggs. Gene expression was tested by protein and mRNA analyses. During an observation period of 18 months, mice were sacrificed and organs subjected to histologic examinations.
Results: Grossly defined hepatocellular carcinomas reproducibly were observed in mice expressing the X-protein, which were investigated through six generations from the age of 11 to 18 months. Among 14 transgenic mice investigated from the age of 11 to 18 months, 12 were found to have hepatocellular carcinoma, grossly or microscopically. The lesion of the hepatocellular carcinoma disclosed a significant increase in the proliferating cell nuclear antigen in the nuclei.
Conclusion: The incidence of hepatocellular carcinoma (86%) in our HBV X transgenic mice may be highly significant, since, except for one case, HBV X-gene transgenic mice produced in other laboratories did not develop liver tumor or any other pathologic phenomena.</abstract><cop>Oxford</cop><pub>Elsevier B.V</pub><pmid>10424292</pmid><doi>10.1016/S0168-8278(99)80172-X</doi><tpages>10</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - virology Enhancer Elements, Genetic Gastroenterology. Liver. Pancreas. Abdomen HBV X-gene Hepatic tumors Hepatitis B Antigens - genetics Hepatitis B virus - genetics Liver - metabolism Liver - pathology Liver - virology Liver Neoplasms - genetics Liver Neoplasms - pathology Liver Neoplasms - virology Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Mice Mice, Transgenic Proliferating cell nuclear antigen Promoter Regions, Genetic Restriction Mapping Reverse Transcriptase Polymerase Chain Reaction Trans-Activators - genetics Transcription, Genetic Transgenic mice Tumors |
| title | Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein |
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