Cyclins and cyclin-dependent kinases: Comparative study of hepatocellular carcinoma versus cirrhosis
Increasing evidence has indicated that perturbation of cyclins is one of the major factors leading to cancer. The aim of this study was not only to investigate various cell cycle-related kinase activities in hepatocellular carcinoma (HCC), but also to analyze the difference of cell cycle-related kin...
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| Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2003-03, Vol.37 (3), p.534-543 |
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| creator | Masaki, Tsutomu Shiratori, Yasushi Rengifo, William Igarashi, Kouichi Yamagata, Michiko Kurokohchi, Kazutaka Uchida, Naohito Miyauchi, Yoshiaki Yoshiji, Hitoshi Watanabe, Seishiro Omata, Masao Kuriyama, Shigeki |
| description | Increasing evidence has indicated that perturbation of cyclins is one of the major factors leading to cancer. The aim of this study was not only to investigate various cell cycle-related kinase activities in hepatocellular carcinoma (HCC), but also to analyze the difference of cell cycle-related kinase activity levels between hepatitis C virus (HCV)-induced HCC and HCV-induced cirrhosis. The protein levels of cyclins D1, E, A, and H, and of cyclin dependent kinase 1 (Cdk1), Cdk2, Cdk4, Cdk6, and Cdk7 in HCC and in surrounding nontumorous cirrhosis were determined by Western blot. The enzymatic activities of cyclins D1, E, A, Cdk1, Cdk4, Cdk6, Cdk7, and Wee1 were measured using in vitro kinase assays. Protein levels and kinase activities of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 were significantly elevated in HCC compared with surrounding cirrhotic tissues. The enhanced cyclin D1-related kinase activity in HCC was accompanied by the up-regulation of Cdk4 activity, but not Cdk6 activity. The kinase activities of Cdk6, Cdk7, and Cdk1 did not differ between HCC and surrounding cirrhotic tissues. In addition, the protein levels and kinase activities of cyclin D1, Cdk4, and cyclin E were higher in poorly differentiated HCC and advanced HCC. In conclusion, the increases of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 play an important role in the development of HCC from cirrhosis. Cyclin D1, Cdk4, and cyclin E activation may be closely related to the histopathologic grade and progression of HCC. (H
EPATOLOGY 2003;37:534-543.) |
| doi_str_mv | 10.1053/jhep.2003.50112 |
| format | Article |
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EPATOLOGY 2003;37:534-543.)</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1053/jhep.2003.50112</identifier><identifier>PMID: 12601350</identifier><identifier>CODEN: HPTLD9</identifier><language>eng</language><publisher>Philadelphia, PA: Elsevier Inc</publisher><subject>Aged ; Biological and medical sciences ; Blotting, Western ; Carcinoma, Hepatocellular - etiology ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; CDC2 Protein Kinase - analysis ; CDC2 Protein Kinase - metabolism ; CDC2-CDC28 Kinases ; Cell Cycle Proteins ; Cyclin A - analysis ; Cyclin A - metabolism ; Cyclin D1 - analysis ; Cyclin D1 - metabolism ; Cyclin E - analysis ; Cyclin E - metabolism ; Cyclin H ; Cyclin-Dependent Kinase 2 ; Cyclin-Dependent Kinase 4 ; Cyclin-Dependent Kinase 6 ; Cyclin-Dependent Kinases - analysis ; Cyclin-Dependent Kinases - metabolism ; Cyclins - analysis ; Cyclins - metabolism ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; Liver Cirrhosis - complications ; Liver Cirrhosis - metabolism ; Liver Cirrhosis - pathology ; Liver Neoplasms - etiology ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Middle Aged ; Nuclear Proteins ; Phosphorylation ; Protein-Serine-Threonine Kinases - analysis ; Protein-Serine-Threonine Kinases - metabolism ; Protein-Tyrosine Kinases - metabolism ; Proto-Oncogene Proteins ; Retinoblastoma Protein - metabolism ; Tumors</subject><ispartof>Hepatology (Baltimore, Md.), 2003-03, Vol.37 (3), p.534-543</ispartof><rights>2003 The American Association for the Study of Liver Diseases</rights><rights>Copyright © 2003 by the American Association for the Study of Liver Diseases</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4649-675e764da24543fa8dea796df49d388323bcf7776746727d34e5ea3f5ac34f7f3</citedby><cites>FETCH-LOGICAL-c4649-675e764da24543fa8dea796df49d388323bcf7776746727d34e5ea3f5ac34f7f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1053%2Fjhep.2003.50112$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1053%2Fjhep.2003.50112$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14618323$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12601350$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Masaki, Tsutomu</creatorcontrib><creatorcontrib>Shiratori, Yasushi</creatorcontrib><creatorcontrib>Rengifo, William</creatorcontrib><creatorcontrib>Igarashi, Kouichi</creatorcontrib><creatorcontrib>Yamagata, Michiko</creatorcontrib><creatorcontrib>Kurokohchi, Kazutaka</creatorcontrib><creatorcontrib>Uchida, Naohito</creatorcontrib><creatorcontrib>Miyauchi, Yoshiaki</creatorcontrib><creatorcontrib>Yoshiji, Hitoshi</creatorcontrib><creatorcontrib>Watanabe, Seishiro</creatorcontrib><creatorcontrib>Omata, Masao</creatorcontrib><creatorcontrib>Kuriyama, Shigeki</creatorcontrib><title>Cyclins and cyclin-dependent kinases: Comparative study of hepatocellular carcinoma versus cirrhosis</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>Increasing evidence has indicated that perturbation of cyclins is one of the major factors leading to cancer. The aim of this study was not only to investigate various cell cycle-related kinase activities in hepatocellular carcinoma (HCC), but also to analyze the difference of cell cycle-related kinase activity levels between hepatitis C virus (HCV)-induced HCC and HCV-induced cirrhosis. The protein levels of cyclins D1, E, A, and H, and of cyclin dependent kinase 1 (Cdk1), Cdk2, Cdk4, Cdk6, and Cdk7 in HCC and in surrounding nontumorous cirrhosis were determined by Western blot. The enzymatic activities of cyclins D1, E, A, Cdk1, Cdk4, Cdk6, Cdk7, and Wee1 were measured using in vitro kinase assays. Protein levels and kinase activities of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 were significantly elevated in HCC compared with surrounding cirrhotic tissues. The enhanced cyclin D1-related kinase activity in HCC was accompanied by the up-regulation of Cdk4 activity, but not Cdk6 activity. The kinase activities of Cdk6, Cdk7, and Cdk1 did not differ between HCC and surrounding cirrhotic tissues. In addition, the protein levels and kinase activities of cyclin D1, Cdk4, and cyclin E were higher in poorly differentiated HCC and advanced HCC. In conclusion, the increases of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 play an important role in the development of HCC from cirrhosis. Cyclin D1, Cdk4, and cyclin E activation may be closely related to the histopathologic grade and progression of HCC. (H
EPATOLOGY 2003;37:534-543.)</description><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Carcinoma, Hepatocellular - etiology</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>CDC2 Protein Kinase - analysis</subject><subject>CDC2 Protein Kinase - metabolism</subject><subject>CDC2-CDC28 Kinases</subject><subject>Cell Cycle Proteins</subject><subject>Cyclin A - analysis</subject><subject>Cyclin A - metabolism</subject><subject>Cyclin D1 - analysis</subject><subject>Cyclin D1 - metabolism</subject><subject>Cyclin E - analysis</subject><subject>Cyclin E - metabolism</subject><subject>Cyclin H</subject><subject>Cyclin-Dependent Kinase 2</subject><subject>Cyclin-Dependent Kinase 4</subject><subject>Cyclin-Dependent Kinase 6</subject><subject>Cyclin-Dependent Kinases - analysis</subject><subject>Cyclin-Dependent Kinases - metabolism</subject><subject>Cyclins - analysis</subject><subject>Cyclins - metabolism</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Humans</subject><subject>Liver Cirrhosis - complications</subject><subject>Liver Cirrhosis - metabolism</subject><subject>Liver Cirrhosis - pathology</subject><subject>Liver Neoplasms - etiology</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nuclear Proteins</subject><subject>Phosphorylation</subject><subject>Protein-Serine-Threonine Kinases - analysis</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Proto-Oncogene Proteins</subject><subject>Retinoblastoma Protein - metabolism</subject><subject>Tumors</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkLtvFDEQh60IlBwhdTrkBrq9-LXrWzp0CiRSJCigtib2WHHYF57dQ_ffs5s76SqUaqb45vH7GLuWYi1FqW-en3BYKyH0uhRSqjO2kqWyhdaleMNWQllR1FLXF-wd0bMQojZqc84upKqEnJkVC9u9b1JHHLrA_UtfBBywC9iN_HfqgJA-823fDpBhTDvkNE5hz_vI59sw9h6bZmogcw_Zp65vge8w00Tcp5yfekr0nr2N0BBeHesl-_X19uf2rnj4_u1---Wh8KYydVHZEm1lAihTGh1hExBsXYVo6qA3G630o4_W2sqayiobtMESQccSvDbRRn3JPh32Drn_MyGNrk20_Acd9hM5q4VZos_gzQH0uSfKGN2QUwt576Rwi1i3iHWLWPcidp74cFw9PbYYTvzR5Ax8PAJAHpqYofOJTpyp5JJg5uoD9zc1uH_trru7_VFKoa3Qoj7N4ixxlzA78gk7jyFl9KMLffpvgH8ld6bd</recordid><startdate>200303</startdate><enddate>200303</enddate><creator>Masaki, Tsutomu</creator><creator>Shiratori, Yasushi</creator><creator>Rengifo, William</creator><creator>Igarashi, Kouichi</creator><creator>Yamagata, Michiko</creator><creator>Kurokohchi, Kazutaka</creator><creator>Uchida, Naohito</creator><creator>Miyauchi, Yoshiaki</creator><creator>Yoshiji, Hitoshi</creator><creator>Watanabe, Seishiro</creator><creator>Omata, Masao</creator><creator>Kuriyama, Shigeki</creator><general>Elsevier Inc</general><general>W.B. Saunders</general><general>Wiley</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>200303</creationdate><title>Cyclins and cyclin-dependent kinases: Comparative study of hepatocellular carcinoma versus cirrhosis</title><author>Masaki, Tsutomu ; Shiratori, Yasushi ; Rengifo, William ; Igarashi, Kouichi ; Yamagata, Michiko ; Kurokohchi, Kazutaka ; Uchida, Naohito ; Miyauchi, Yoshiaki ; Yoshiji, Hitoshi ; Watanabe, Seishiro ; Omata, Masao ; Kuriyama, Shigeki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4649-675e764da24543fa8dea796df49d388323bcf7776746727d34e5ea3f5ac34f7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Carcinoma, Hepatocellular - etiology</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>CDC2 Protein Kinase - analysis</topic><topic>CDC2 Protein Kinase - metabolism</topic><topic>CDC2-CDC28 Kinases</topic><topic>Cell Cycle Proteins</topic><topic>Cyclin A - analysis</topic><topic>Cyclin A - metabolism</topic><topic>Cyclin D1 - analysis</topic><topic>Cyclin D1 - metabolism</topic><topic>Cyclin E - analysis</topic><topic>Cyclin E - metabolism</topic><topic>Cyclin H</topic><topic>Cyclin-Dependent Kinase 2</topic><topic>Cyclin-Dependent Kinase 4</topic><topic>Cyclin-Dependent Kinase 6</topic><topic>Cyclin-Dependent Kinases - analysis</topic><topic>Cyclin-Dependent Kinases - metabolism</topic><topic>Cyclins - analysis</topic><topic>Cyclins - metabolism</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Humans</topic><topic>Liver Cirrhosis - complications</topic><topic>Liver Cirrhosis - metabolism</topic><topic>Liver Cirrhosis - pathology</topic><topic>Liver Neoplasms - etiology</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nuclear Proteins</topic><topic>Phosphorylation</topic><topic>Protein-Serine-Threonine Kinases - analysis</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Proto-Oncogene Proteins</topic><topic>Retinoblastoma Protein - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Masaki, Tsutomu</creatorcontrib><creatorcontrib>Shiratori, Yasushi</creatorcontrib><creatorcontrib>Rengifo, William</creatorcontrib><creatorcontrib>Igarashi, Kouichi</creatorcontrib><creatorcontrib>Yamagata, Michiko</creatorcontrib><creatorcontrib>Kurokohchi, Kazutaka</creatorcontrib><creatorcontrib>Uchida, Naohito</creatorcontrib><creatorcontrib>Miyauchi, Yoshiaki</creatorcontrib><creatorcontrib>Yoshiji, Hitoshi</creatorcontrib><creatorcontrib>Watanabe, Seishiro</creatorcontrib><creatorcontrib>Omata, Masao</creatorcontrib><creatorcontrib>Kuriyama, Shigeki</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>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Masaki, Tsutomu</au><au>Shiratori, Yasushi</au><au>Rengifo, William</au><au>Igarashi, Kouichi</au><au>Yamagata, Michiko</au><au>Kurokohchi, Kazutaka</au><au>Uchida, Naohito</au><au>Miyauchi, Yoshiaki</au><au>Yoshiji, Hitoshi</au><au>Watanabe, Seishiro</au><au>Omata, Masao</au><au>Kuriyama, Shigeki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cyclins and cyclin-dependent kinases: Comparative study of hepatocellular carcinoma versus cirrhosis</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2003-03</date><risdate>2003</risdate><volume>37</volume><issue>3</issue><spage>534</spage><epage>543</epage><pages>534-543</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><abstract>Increasing evidence has indicated that perturbation of cyclins is one of the major factors leading to cancer. The aim of this study was not only to investigate various cell cycle-related kinase activities in hepatocellular carcinoma (HCC), but also to analyze the difference of cell cycle-related kinase activity levels between hepatitis C virus (HCV)-induced HCC and HCV-induced cirrhosis. The protein levels of cyclins D1, E, A, and H, and of cyclin dependent kinase 1 (Cdk1), Cdk2, Cdk4, Cdk6, and Cdk7 in HCC and in surrounding nontumorous cirrhosis were determined by Western blot. The enzymatic activities of cyclins D1, E, A, Cdk1, Cdk4, Cdk6, Cdk7, and Wee1 were measured using in vitro kinase assays. Protein levels and kinase activities of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 were significantly elevated in HCC compared with surrounding cirrhotic tissues. The enhanced cyclin D1-related kinase activity in HCC was accompanied by the up-regulation of Cdk4 activity, but not Cdk6 activity. The kinase activities of Cdk6, Cdk7, and Cdk1 did not differ between HCC and surrounding cirrhotic tissues. In addition, the protein levels and kinase activities of cyclin D1, Cdk4, and cyclin E were higher in poorly differentiated HCC and advanced HCC. In conclusion, the increases of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 play an important role in the development of HCC from cirrhosis. Cyclin D1, Cdk4, and cyclin E activation may be closely related to the histopathologic grade and progression of HCC. (H
EPATOLOGY 2003;37:534-543.)</abstract><cop>Philadelphia, PA</cop><pub>Elsevier Inc</pub><pmid>12601350</pmid><doi>10.1053/jhep.2003.50112</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Biological and medical sciences Blotting, Western Carcinoma, Hepatocellular - etiology Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology CDC2 Protein Kinase - analysis CDC2 Protein Kinase - metabolism CDC2-CDC28 Kinases Cell Cycle Proteins Cyclin A - analysis Cyclin A - metabolism Cyclin D1 - analysis Cyclin D1 - metabolism Cyclin E - analysis Cyclin E - metabolism Cyclin H Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase 6 Cyclin-Dependent Kinases - analysis Cyclin-Dependent Kinases - metabolism Cyclins - analysis Cyclins - metabolism Female Gastroenterology. Liver. Pancreas. Abdomen Humans Liver Cirrhosis - complications Liver Cirrhosis - metabolism Liver Cirrhosis - pathology Liver Neoplasms - etiology Liver Neoplasms - metabolism Liver Neoplasms - pathology Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Middle Aged Nuclear Proteins Phosphorylation Protein-Serine-Threonine Kinases - analysis Protein-Serine-Threonine Kinases - metabolism Protein-Tyrosine Kinases - metabolism Proto-Oncogene Proteins Retinoblastoma Protein - metabolism Tumors |
| title | Cyclins and cyclin-dependent kinases: Comparative study of hepatocellular carcinoma versus cirrhosis |
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