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Parkin gene alterations in hepatocellular carcinoma
The Parkin gene is an extremely large gene (1.5 Mb) within the highly unstable FRA6E common fragile site (CFS) region, which is frequently altered in ovarian, breast, and hepatocellular carcinomas. Because Parkin/FRA6E has genomic similarities to FHIT/FRA3B and WWOX/FRA16D, two other large tumor‐sup...
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| Published in: | Genes chromosomes & cancer 2004-06, Vol.40 (2), p.85-96 |
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| cited_by | cdi_FETCH-LOGICAL-c4560-81d082d76f27967fe685dc81a9de9372246fb600a5c71d1a68881bea0334a2fc3 |
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| cites | cdi_FETCH-LOGICAL-c4560-81d082d76f27967fe685dc81a9de9372246fb600a5c71d1a68881bea0334a2fc3 |
| container_end_page | 96 |
| container_issue | 2 |
| container_start_page | 85 |
| container_title | Genes chromosomes & cancer |
| container_volume | 40 |
| creator | Wang, Fang Denison, Stacy Lai, Jin-Ping Philips, Leslie A. Montoya, Damien Kock, Norman Schüle, Birgitt Klein, Christine Shridhar, Viji Roberts, Lewis R. Smith, David I. |
| description | The Parkin gene is an extremely large gene (1.5 Mb) within the highly unstable FRA6E common fragile site (CFS) region, which is frequently altered in ovarian, breast, and hepatocellular carcinomas. Because Parkin/FRA6E has genomic similarities to FHIT/FRA3B and WWOX/FRA16D, two other large tumor‐suppressor genes that are within CFS regions, we were interested in characterizing Parkin gene alterations and their possible association with cancer. After analyzing 50 cancer‐derived cell lines including 11 hepatocellular carcinoma (HCC) cell lines, we found that one HCC cell line, PLC/PRF/5, had a detectable homozygous deletion encompassing exon 3. Using quantitative duplex PCR and fluorescence in situ hybridization analysis to characterize the copy number changes of Parkin exons in HCC cell lines, we found that 4 of 11 HCC cell lines had heterozygous deletions of Parkin exons and one, Hep3B, had an exon duplication. Parkin protein expression was significantly decreased or absent in all 11 HCC cell lines. Furthermore, more than 50% of HCC primary tumors had decreased Parkin expression compared to that in normal liver tissue. Parkin gene–transfected PLC5 and Hep3B cells grew more slowly than vector‐only transfectants and also showed increased sensitivity to apoptosis induced by cell‐cycle inhibitors. Therefore, we suggest that Parkin may be involved in tumor suppression and that the loss of Parkin contributes to the development of hepatocarcinoma. © 2004 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/gcc.20020 |
| format | article |
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Because Parkin/FRA6E has genomic similarities to FHIT/FRA3B and WWOX/FRA16D, two other large tumor‐suppressor genes that are within CFS regions, we were interested in characterizing Parkin gene alterations and their possible association with cancer. After analyzing 50 cancer‐derived cell lines including 11 hepatocellular carcinoma (HCC) cell lines, we found that one HCC cell line, PLC/PRF/5, had a detectable homozygous deletion encompassing exon 3. Using quantitative duplex PCR and fluorescence in situ hybridization analysis to characterize the copy number changes of Parkin exons in HCC cell lines, we found that 4 of 11 HCC cell lines had heterozygous deletions of Parkin exons and one, Hep3B, had an exon duplication. Parkin protein expression was significantly decreased or absent in all 11 HCC cell lines. Furthermore, more than 50% of HCC primary tumors had decreased Parkin expression compared to that in normal liver tissue. Parkin gene–transfected PLC5 and Hep3B cells grew more slowly than vector‐only transfectants and also showed increased sensitivity to apoptosis induced by cell‐cycle inhibitors. Therefore, we suggest that Parkin may be involved in tumor suppression and that the loss of Parkin contributes to the development of hepatocarcinoma. © 2004 Wiley‐Liss, Inc.</description><identifier>ISSN: 1045-2257</identifier><identifier>EISSN: 1098-2264</identifier><identifier>DOI: 10.1002/gcc.20020</identifier><identifier>PMID: 15101042</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Apoptosis - genetics ; Apoptosis - physiology ; Blotting, Western - methods ; Carcinoma, Hepatocellular - chemistry ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - pathology ; Cell Division - genetics ; Cell Division - physiology ; Chromosome Deletion ; DNA, Neoplasm - genetics ; Exons - genetics ; Gene Dosage ; Genes, Tumor Suppressor - physiology ; Homozygote ; Humans ; Immunohistochemistry - methods ; In Situ Hybridization, Fluorescence - methods ; Liver Neoplasms - chemistry ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Polymerase Chain Reaction - methods ; RNA, Neoplasm - genetics ; Transfection ; Tumor Cells, Cultured ; Ubiquitin-Protein Ligases - biosynthesis ; Ubiquitin-Protein Ligases - genetics ; Ubiquitin-Protein Ligases - immunology ; Ubiquitin-Protein Ligases - physiology</subject><ispartof>Genes chromosomes & cancer, 2004-06, Vol.40 (2), p.85-96</ispartof><rights>Copyright © 2004 Wiley‐Liss, Inc.</rights><rights>Copyright 2004 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4560-81d082d76f27967fe685dc81a9de9372246fb600a5c71d1a68881bea0334a2fc3</citedby><cites>FETCH-LOGICAL-c4560-81d082d76f27967fe685dc81a9de9372246fb600a5c71d1a68881bea0334a2fc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,783,787,27937,27938</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15101042$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Fang</creatorcontrib><creatorcontrib>Denison, Stacy</creatorcontrib><creatorcontrib>Lai, Jin-Ping</creatorcontrib><creatorcontrib>Philips, Leslie A.</creatorcontrib><creatorcontrib>Montoya, Damien</creatorcontrib><creatorcontrib>Kock, Norman</creatorcontrib><creatorcontrib>Schüle, Birgitt</creatorcontrib><creatorcontrib>Klein, Christine</creatorcontrib><creatorcontrib>Shridhar, Viji</creatorcontrib><creatorcontrib>Roberts, Lewis R.</creatorcontrib><creatorcontrib>Smith, David I.</creatorcontrib><title>Parkin gene alterations in hepatocellular carcinoma</title><title>Genes chromosomes & cancer</title><addtitle>Genes Chromosom. Cancer</addtitle><description>The Parkin gene is an extremely large gene (1.5 Mb) within the highly unstable FRA6E common fragile site (CFS) region, which is frequently altered in ovarian, breast, and hepatocellular carcinomas. Because Parkin/FRA6E has genomic similarities to FHIT/FRA3B and WWOX/FRA16D, two other large tumor‐suppressor genes that are within CFS regions, we were interested in characterizing Parkin gene alterations and their possible association with cancer. After analyzing 50 cancer‐derived cell lines including 11 hepatocellular carcinoma (HCC) cell lines, we found that one HCC cell line, PLC/PRF/5, had a detectable homozygous deletion encompassing exon 3. Using quantitative duplex PCR and fluorescence in situ hybridization analysis to characterize the copy number changes of Parkin exons in HCC cell lines, we found that 4 of 11 HCC cell lines had heterozygous deletions of Parkin exons and one, Hep3B, had an exon duplication. Parkin protein expression was significantly decreased or absent in all 11 HCC cell lines. Furthermore, more than 50% of HCC primary tumors had decreased Parkin expression compared to that in normal liver tissue. Parkin gene–transfected PLC5 and Hep3B cells grew more slowly than vector‐only transfectants and also showed increased sensitivity to apoptosis induced by cell‐cycle inhibitors. Therefore, we suggest that Parkin may be involved in tumor suppression and that the loss of Parkin contributes to the development of hepatocarcinoma. © 2004 Wiley‐Liss, Inc.</description><subject>Apoptosis - genetics</subject><subject>Apoptosis - physiology</subject><subject>Blotting, Western - methods</subject><subject>Carcinoma, Hepatocellular - chemistry</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell Division - genetics</subject><subject>Cell Division - physiology</subject><subject>Chromosome Deletion</subject><subject>DNA, Neoplasm - genetics</subject><subject>Exons - genetics</subject><subject>Gene Dosage</subject><subject>Genes, Tumor Suppressor - physiology</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Immunohistochemistry - methods</subject><subject>In Situ Hybridization, Fluorescence - methods</subject><subject>Liver Neoplasms - chemistry</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Polymerase Chain Reaction - methods</subject><subject>RNA, Neoplasm - genetics</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><subject>Ubiquitin-Protein Ligases - biosynthesis</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><subject>Ubiquitin-Protein Ligases - immunology</subject><subject>Ubiquitin-Protein Ligases - physiology</subject><issn>1045-2257</issn><issn>1098-2264</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNqFkU1LAzEQhoMoVqsH_4DsSfCw7STZfOxRqm2F4gcqgpeQZrN1dT9qskX7701t1ZN4mpeZZ16GdxA6wtDDAKQ_M6ZHgoAttIchlTEhPNle6YQFzUQH7Xv_AgCcpmwXdTDDEIZkD9Eb7V6LOprZ2ka6bK3TbdHUPgq9ZzvXbWNsWS5K7SKjnSnqptIHaCfXpbeHm9pFD8OL-8E4nlyPLgdnk9gkjEMscQaSZILnRKRc5JZLlhmJdZrZlApCEp5POYBmRuAMay6lxFOrgdJEk9zQLjpZ-85d87awvlVV4Vfn6No2C68ElgxSQv8FsRCMMsYCeLoGjWu8dzZXc1dU2i0VBrWKUoUo1VeUgT3emC6mlc1-yU12AeivgfeitMu_ndRoMPi2jNcbhW_tx89G-IDiggqmHq9G6m5yPh6Kp1sl6SdeCYqA</recordid><startdate>200406</startdate><enddate>200406</enddate><creator>Wang, Fang</creator><creator>Denison, Stacy</creator><creator>Lai, Jin-Ping</creator><creator>Philips, Leslie A.</creator><creator>Montoya, Damien</creator><creator>Kock, Norman</creator><creator>Schüle, Birgitt</creator><creator>Klein, Christine</creator><creator>Shridhar, Viji</creator><creator>Roberts, Lewis R.</creator><creator>Smith, David I.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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><scope>7X8</scope></search><sort><creationdate>200406</creationdate><title>Parkin gene alterations in hepatocellular carcinoma</title><author>Wang, Fang ; Denison, Stacy ; Lai, Jin-Ping ; Philips, Leslie A. ; Montoya, Damien ; Kock, Norman ; Schüle, Birgitt ; Klein, Christine ; Shridhar, Viji ; Roberts, Lewis R. ; Smith, David I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4560-81d082d76f27967fe685dc81a9de9372246fb600a5c71d1a68881bea0334a2fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Apoptosis - genetics</topic><topic>Apoptosis - physiology</topic><topic>Blotting, Western - methods</topic><topic>Carcinoma, Hepatocellular - chemistry</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell Division - genetics</topic><topic>Cell Division - physiology</topic><topic>Chromosome Deletion</topic><topic>DNA, Neoplasm - genetics</topic><topic>Exons - genetics</topic><topic>Gene Dosage</topic><topic>Genes, Tumor Suppressor - physiology</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Immunohistochemistry - methods</topic><topic>In Situ Hybridization, Fluorescence - methods</topic><topic>Liver Neoplasms - chemistry</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - pathology</topic><topic>Polymerase Chain Reaction - methods</topic><topic>RNA, Neoplasm - genetics</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><topic>Ubiquitin-Protein Ligases - biosynthesis</topic><topic>Ubiquitin-Protein Ligases - genetics</topic><topic>Ubiquitin-Protein Ligases - immunology</topic><topic>Ubiquitin-Protein Ligases - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Fang</creatorcontrib><creatorcontrib>Denison, Stacy</creatorcontrib><creatorcontrib>Lai, Jin-Ping</creatorcontrib><creatorcontrib>Philips, Leslie A.</creatorcontrib><creatorcontrib>Montoya, Damien</creatorcontrib><creatorcontrib>Kock, Norman</creatorcontrib><creatorcontrib>Schüle, Birgitt</creatorcontrib><creatorcontrib>Klein, Christine</creatorcontrib><creatorcontrib>Shridhar, Viji</creatorcontrib><creatorcontrib>Roberts, Lewis R.</creatorcontrib><creatorcontrib>Smith, David I.</creatorcontrib><collection>Istex</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><collection>MEDLINE - Academic</collection><jtitle>Genes chromosomes & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Fang</au><au>Denison, Stacy</au><au>Lai, Jin-Ping</au><au>Philips, Leslie A.</au><au>Montoya, Damien</au><au>Kock, Norman</au><au>Schüle, Birgitt</au><au>Klein, Christine</au><au>Shridhar, Viji</au><au>Roberts, Lewis R.</au><au>Smith, David I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Parkin gene alterations in hepatocellular carcinoma</atitle><jtitle>Genes chromosomes & cancer</jtitle><addtitle>Genes Chromosom. Cancer</addtitle><date>2004-06</date><risdate>2004</risdate><volume>40</volume><issue>2</issue><spage>85</spage><epage>96</epage><pages>85-96</pages><issn>1045-2257</issn><eissn>1098-2264</eissn><abstract>The Parkin gene is an extremely large gene (1.5 Mb) within the highly unstable FRA6E common fragile site (CFS) region, which is frequently altered in ovarian, breast, and hepatocellular carcinomas. Because Parkin/FRA6E has genomic similarities to FHIT/FRA3B and WWOX/FRA16D, two other large tumor‐suppressor genes that are within CFS regions, we were interested in characterizing Parkin gene alterations and their possible association with cancer. After analyzing 50 cancer‐derived cell lines including 11 hepatocellular carcinoma (HCC) cell lines, we found that one HCC cell line, PLC/PRF/5, had a detectable homozygous deletion encompassing exon 3. Using quantitative duplex PCR and fluorescence in situ hybridization analysis to characterize the copy number changes of Parkin exons in HCC cell lines, we found that 4 of 11 HCC cell lines had heterozygous deletions of Parkin exons and one, Hep3B, had an exon duplication. Parkin protein expression was significantly decreased or absent in all 11 HCC cell lines. Furthermore, more than 50% of HCC primary tumors had decreased Parkin expression compared to that in normal liver tissue. Parkin gene–transfected PLC5 and Hep3B cells grew more slowly than vector‐only transfectants and also showed increased sensitivity to apoptosis induced by cell‐cycle inhibitors. Therefore, we suggest that Parkin may be involved in tumor suppression and that the loss of Parkin contributes to the development of hepatocarcinoma. © 2004 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15101042</pmid><doi>10.1002/gcc.20020</doi><tpages>12</tpages></addata></record> |
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| subjects | Apoptosis - genetics Apoptosis - physiology Blotting, Western - methods Carcinoma, Hepatocellular - chemistry Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - pathology Cell Division - genetics Cell Division - physiology Chromosome Deletion DNA, Neoplasm - genetics Exons - genetics Gene Dosage Genes, Tumor Suppressor - physiology Homozygote Humans Immunohistochemistry - methods In Situ Hybridization, Fluorescence - methods Liver Neoplasms - chemistry Liver Neoplasms - genetics Liver Neoplasms - pathology Polymerase Chain Reaction - methods RNA, Neoplasm - genetics Transfection Tumor Cells, Cultured Ubiquitin-Protein Ligases - biosynthesis Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - immunology Ubiquitin-Protein Ligases - physiology |
| title | Parkin gene alterations in hepatocellular carcinoma |
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