The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma
BACKGROUND Loss of the cell‐cycle inhibitory protein p27Kip1 is associated with poor prognosis in colorectal carcinoma. The decrease in p27Kip1 levels is the result of increased proteasome‐dependent degradation, mediated and rate‐limited by its specific ubiquitin ligase subunits S‐phase kinase prote...
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| Veröffentlicht in: | Cancer 2005-04, Vol.103 (7), p.1336-1346 |
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| creator | Shapira, Ma'anit Ben–Izhak, Ofer Linn, Shai Futerman, Boris Minkov, Ira Hershko, Dan D. |
| description | BACKGROUND
Loss of the cell‐cycle inhibitory protein p27Kip1 is associated with poor prognosis in colorectal carcinoma. The decrease in p27Kip1 levels is the result of increased proteasome‐dependent degradation, mediated and rate‐limited by its specific ubiquitin ligase subunits S‐phase kinase protein (Skp) 2 and cyclin‐dependent kinase subunit (Cks) 1. Recently, Skp2 and Cks1 expression were found to be increased in some colorectal carcinomas, but their potential role as prognostic markers for survival is unknown. The present study was undertaken to assess the prognostic value of both Skp2 and Cks1 in colorectal carcinoma.
MATERIALS AND METHODS
The expression of Skp2, Cks1, and p27Kip1 was examined by immunohistochemistry using highly specific antibodies on formalin‐fixed, paraffin‐embedded tissue sections from 80 patients with colorectal carcinoma.
RESULTS
Overexpression of Skp2 and Cks1 strongly correlated with loss of p27Kip1 and loss of tumor differentiation. A significant decrease in overall survival was observed in patients expressing high Skp2 or Cks1 levels, and in particular, patients with Stage II and III disease. Each protein provided significant additional prognostic information to that given by disease stage, tumor grade, or p27Kip1 expression.
CONCLUSIONS
Results suggest that overexpression of Skp2 or Cks1 is strongly associated with poor prognosis and may thus be used as prognostic markers for overall survival in colorectal carcinoma. Cancer 2005. © 2005 American Cancer Society.
The expression of S‐phase kinase‐associated protein 2 (Skp2) and cyclin kinase subunit 1 (Cks1), the specific ubiquitin ligase subunits that target p27Kip1 for degradation, are altered in various human cancers. It is shown in the current study that increased expression of Skp2 or Cks1 is strongly associated with poor prognosis and that their increased expression may be used as a prognostic marker for overall survival in colorectal carcinoma. |
| doi_str_mv | 10.1002/cncr.20917 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67547916</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>67547916</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4597-8431f9b767d8d3063bbb4217f4fe8af732d64c836c0ef5a8f9198560f71f51203</originalsourceid><addsrcrecordid>eNp9kEtLxDAUhYMozji68QdINroQOubRJu1Sii8YFHQEF0JJ02SM09ckLTL_3owtzM7V5XI_zjn3AHCO0RwjRG5kLe2coATzAzDFKOEBwiE5BFOEUBxEIf2YgBPnvv3KSUSPwQRHHHNKyBR8Lr8UbG2zqhvXGQlN1QrZwUbDzh_63Gx605kalmYlnIKuz_vadA6-rVsCRV3AdO0w9IBsysYq2YkSSmGlqZtKnIIjLUqnzsY5A-_3d8v0MVi8PDylt4tAhpFPG4cU6yTnjBdxQRGjeZ6HBHMdahUL7YMWLJQxZRIpHYlYJziJI4Y0xzrCBNEZuBp0_SObXrkuq4yTqixFrZreZYxHIU8w8-D1AErbOGeVzlprKmG3GUbZrsts12X216WHL0bVPq9UsUfH8jxwOQLCSVFqK2pp3J5jjHqhXTw8cD-mVNt_LLP0OX0dzH8B0smLTg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67547916</pqid></control><display><type>article</type><title>The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma</title><source>MEDLINE</source><source>Wiley Free Archive</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Alma/SFX Local Collection</source><source>EZB Electronic Journals Library</source><creator>Shapira, Ma'anit ; Ben–Izhak, Ofer ; Linn, Shai ; Futerman, Boris ; Minkov, Ira ; Hershko, Dan D.</creator><creatorcontrib>Shapira, Ma'anit ; Ben–Izhak, Ofer ; Linn, Shai ; Futerman, Boris ; Minkov, Ira ; Hershko, Dan D.</creatorcontrib><description>BACKGROUND
Loss of the cell‐cycle inhibitory protein p27Kip1 is associated with poor prognosis in colorectal carcinoma. The decrease in p27Kip1 levels is the result of increased proteasome‐dependent degradation, mediated and rate‐limited by its specific ubiquitin ligase subunits S‐phase kinase protein (Skp) 2 and cyclin‐dependent kinase subunit (Cks) 1. Recently, Skp2 and Cks1 expression were found to be increased in some colorectal carcinomas, but their potential role as prognostic markers for survival is unknown. The present study was undertaken to assess the prognostic value of both Skp2 and Cks1 in colorectal carcinoma.
MATERIALS AND METHODS
The expression of Skp2, Cks1, and p27Kip1 was examined by immunohistochemistry using highly specific antibodies on formalin‐fixed, paraffin‐embedded tissue sections from 80 patients with colorectal carcinoma.
RESULTS
Overexpression of Skp2 and Cks1 strongly correlated with loss of p27Kip1 and loss of tumor differentiation. A significant decrease in overall survival was observed in patients expressing high Skp2 or Cks1 levels, and in particular, patients with Stage II and III disease. Each protein provided significant additional prognostic information to that given by disease stage, tumor grade, or p27Kip1 expression.
CONCLUSIONS
Results suggest that overexpression of Skp2 or Cks1 is strongly associated with poor prognosis and may thus be used as prognostic markers for overall survival in colorectal carcinoma. Cancer 2005. © 2005 American Cancer Society.
The expression of S‐phase kinase‐associated protein 2 (Skp2) and cyclin kinase subunit 1 (Cks1), the specific ubiquitin ligase subunits that target p27Kip1 for degradation, are altered in various human cancers. It is shown in the current study that increased expression of Skp2 or Cks1 is strongly associated with poor prognosis and that their increased expression may be used as a prognostic marker for overall survival in colorectal carcinoma.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/cncr.20917</identifier><identifier>PMID: 15717322</identifier><identifier>CODEN: CANCAR</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Aged ; Biological and medical sciences ; Biomarkers, Tumor ; Cell Cycle Proteins - metabolism ; Cell Differentiation ; Cks1 ; colorectal carcinoma ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - mortality ; Colorectal Neoplasms - pathology ; cyclin kinase subunit 1 ; Cyclin-Dependent Kinase Inhibitor p27 ; Cyclin-Dependent Kinases - metabolism ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; Immunohistochemistry ; Male ; Medical sciences ; p27Kip1 ; Prognosis ; S-Phase Kinase-Associated Proteins - metabolism ; Skp2 ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Survival Analysis ; S‐phase kinase‐associated protein 2 ; Tumor Suppressor Proteins - metabolism ; Tumors ; ubiquitin</subject><ispartof>Cancer, 2005-04, Vol.103 (7), p.1336-1346</ispartof><rights>Copyright © 2005 American Cancer Society</rights><rights>2005 INIST-CNRS</rights><rights>Copyright 2005 American Cancer Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4597-8431f9b767d8d3063bbb4217f4fe8af732d64c836c0ef5a8f9198560f71f51203</citedby><cites>FETCH-LOGICAL-c4597-8431f9b767d8d3063bbb4217f4fe8af732d64c836c0ef5a8f9198560f71f51203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcncr.20917$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcncr.20917$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16630910$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15717322$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shapira, Ma'anit</creatorcontrib><creatorcontrib>Ben–Izhak, Ofer</creatorcontrib><creatorcontrib>Linn, Shai</creatorcontrib><creatorcontrib>Futerman, Boris</creatorcontrib><creatorcontrib>Minkov, Ira</creatorcontrib><creatorcontrib>Hershko, Dan D.</creatorcontrib><title>The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma</title><title>Cancer</title><addtitle>Cancer</addtitle><description>BACKGROUND
Loss of the cell‐cycle inhibitory protein p27Kip1 is associated with poor prognosis in colorectal carcinoma. The decrease in p27Kip1 levels is the result of increased proteasome‐dependent degradation, mediated and rate‐limited by its specific ubiquitin ligase subunits S‐phase kinase protein (Skp) 2 and cyclin‐dependent kinase subunit (Cks) 1. Recently, Skp2 and Cks1 expression were found to be increased in some colorectal carcinomas, but their potential role as prognostic markers for survival is unknown. The present study was undertaken to assess the prognostic value of both Skp2 and Cks1 in colorectal carcinoma.
MATERIALS AND METHODS
The expression of Skp2, Cks1, and p27Kip1 was examined by immunohistochemistry using highly specific antibodies on formalin‐fixed, paraffin‐embedded tissue sections from 80 patients with colorectal carcinoma.
RESULTS
Overexpression of Skp2 and Cks1 strongly correlated with loss of p27Kip1 and loss of tumor differentiation. A significant decrease in overall survival was observed in patients expressing high Skp2 or Cks1 levels, and in particular, patients with Stage II and III disease. Each protein provided significant additional prognostic information to that given by disease stage, tumor grade, or p27Kip1 expression.
CONCLUSIONS
Results suggest that overexpression of Skp2 or Cks1 is strongly associated with poor prognosis and may thus be used as prognostic markers for overall survival in colorectal carcinoma. Cancer 2005. © 2005 American Cancer Society.
The expression of S‐phase kinase‐associated protein 2 (Skp2) and cyclin kinase subunit 1 (Cks1), the specific ubiquitin ligase subunits that target p27Kip1 for degradation, are altered in various human cancers. It is shown in the current study that increased expression of Skp2 or Cks1 is strongly associated with poor prognosis and that their increased expression may be used as a prognostic marker for overall survival in colorectal carcinoma.</description><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Differentiation</subject><subject>Cks1</subject><subject>colorectal carcinoma</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Colorectal Neoplasms - pathology</subject><subject>cyclin kinase subunit 1</subject><subject>Cyclin-Dependent Kinase Inhibitor p27</subject><subject>Cyclin-Dependent Kinases - metabolism</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Medical sciences</subject><subject>p27Kip1</subject><subject>Prognosis</subject><subject>S-Phase Kinase-Associated Proteins - metabolism</subject><subject>Skp2</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Survival Analysis</subject><subject>S‐phase kinase‐associated protein 2</subject><subject>Tumor Suppressor Proteins - metabolism</subject><subject>Tumors</subject><subject>ubiquitin</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLxDAUhYMozji68QdINroQOubRJu1Sii8YFHQEF0JJ02SM09ckLTL_3owtzM7V5XI_zjn3AHCO0RwjRG5kLe2coATzAzDFKOEBwiE5BFOEUBxEIf2YgBPnvv3KSUSPwQRHHHNKyBR8Lr8UbG2zqhvXGQlN1QrZwUbDzh_63Gx605kalmYlnIKuz_vadA6-rVsCRV3AdO0w9IBsysYq2YkSSmGlqZtKnIIjLUqnzsY5A-_3d8v0MVi8PDylt4tAhpFPG4cU6yTnjBdxQRGjeZ6HBHMdahUL7YMWLJQxZRIpHYlYJziJI4Y0xzrCBNEZuBp0_SObXrkuq4yTqixFrZreZYxHIU8w8-D1AErbOGeVzlprKmG3GUbZrsts12X216WHL0bVPq9UsUfH8jxwOQLCSVFqK2pp3J5jjHqhXTw8cD-mVNt_LLP0OX0dzH8B0smLTg</recordid><startdate>20050401</startdate><enddate>20050401</enddate><creator>Shapira, Ma'anit</creator><creator>Ben–Izhak, Ofer</creator><creator>Linn, Shai</creator><creator>Futerman, Boris</creator><creator>Minkov, Ira</creator><creator>Hershko, Dan D.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</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>20050401</creationdate><title>The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma</title><author>Shapira, Ma'anit ; Ben–Izhak, Ofer ; Linn, Shai ; Futerman, Boris ; Minkov, Ira ; Hershko, Dan D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4597-8431f9b767d8d3063bbb4217f4fe8af732d64c836c0ef5a8f9198560f71f51203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Differentiation</topic><topic>Cks1</topic><topic>colorectal carcinoma</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - mortality</topic><topic>Colorectal Neoplasms - pathology</topic><topic>cyclin kinase subunit 1</topic><topic>Cyclin-Dependent Kinase Inhibitor p27</topic><topic>Cyclin-Dependent Kinases - metabolism</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Medical sciences</topic><topic>p27Kip1</topic><topic>Prognosis</topic><topic>S-Phase Kinase-Associated Proteins - metabolism</topic><topic>Skp2</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Survival Analysis</topic><topic>S‐phase kinase‐associated protein 2</topic><topic>Tumor Suppressor Proteins - metabolism</topic><topic>Tumors</topic><topic>ubiquitin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shapira, Ma'anit</creatorcontrib><creatorcontrib>Ben–Izhak, Ofer</creatorcontrib><creatorcontrib>Linn, Shai</creatorcontrib><creatorcontrib>Futerman, Boris</creatorcontrib><creatorcontrib>Minkov, Ira</creatorcontrib><creatorcontrib>Hershko, Dan D.</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>Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shapira, Ma'anit</au><au>Ben–Izhak, Ofer</au><au>Linn, Shai</au><au>Futerman, Boris</au><au>Minkov, Ira</au><au>Hershko, Dan D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma</atitle><jtitle>Cancer</jtitle><addtitle>Cancer</addtitle><date>2005-04-01</date><risdate>2005</risdate><volume>103</volume><issue>7</issue><spage>1336</spage><epage>1346</epage><pages>1336-1346</pages><issn>0008-543X</issn><eissn>1097-0142</eissn><coden>CANCAR</coden><abstract>BACKGROUND
Loss of the cell‐cycle inhibitory protein p27Kip1 is associated with poor prognosis in colorectal carcinoma. The decrease in p27Kip1 levels is the result of increased proteasome‐dependent degradation, mediated and rate‐limited by its specific ubiquitin ligase subunits S‐phase kinase protein (Skp) 2 and cyclin‐dependent kinase subunit (Cks) 1. Recently, Skp2 and Cks1 expression were found to be increased in some colorectal carcinomas, but their potential role as prognostic markers for survival is unknown. The present study was undertaken to assess the prognostic value of both Skp2 and Cks1 in colorectal carcinoma.
MATERIALS AND METHODS
The expression of Skp2, Cks1, and p27Kip1 was examined by immunohistochemistry using highly specific antibodies on formalin‐fixed, paraffin‐embedded tissue sections from 80 patients with colorectal carcinoma.
RESULTS
Overexpression of Skp2 and Cks1 strongly correlated with loss of p27Kip1 and loss of tumor differentiation. A significant decrease in overall survival was observed in patients expressing high Skp2 or Cks1 levels, and in particular, patients with Stage II and III disease. Each protein provided significant additional prognostic information to that given by disease stage, tumor grade, or p27Kip1 expression.
CONCLUSIONS
Results suggest that overexpression of Skp2 or Cks1 is strongly associated with poor prognosis and may thus be used as prognostic markers for overall survival in colorectal carcinoma. Cancer 2005. © 2005 American Cancer Society.
The expression of S‐phase kinase‐associated protein 2 (Skp2) and cyclin kinase subunit 1 (Cks1), the specific ubiquitin ligase subunits that target p27Kip1 for degradation, are altered in various human cancers. It is shown in the current study that increased expression of Skp2 or Cks1 is strongly associated with poor prognosis and that their increased expression may be used as a prognostic marker for overall survival in colorectal carcinoma.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15717322</pmid><doi>10.1002/cncr.20917</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Biological and medical sciences Biomarkers, Tumor Cell Cycle Proteins - metabolism Cell Differentiation Cks1 colorectal carcinoma Colorectal Neoplasms - metabolism Colorectal Neoplasms - mortality Colorectal Neoplasms - pathology cyclin kinase subunit 1 Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases - metabolism Female Gastroenterology. Liver. Pancreas. Abdomen Humans Immunohistochemistry Male Medical sciences p27Kip1 Prognosis S-Phase Kinase-Associated Proteins - metabolism Skp2 Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Survival Analysis S‐phase kinase‐associated protein 2 Tumor Suppressor Proteins - metabolism Tumors ubiquitin |
| title | The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma |
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