The Expression of Phospho-AKT, Phospho-mTOR, and PTEN in Extrahepatic Cholangiocarcinoma
Purpose: The protein kinase B (AKT) pathway plays a key role in the regulation of cellular survival, apoptosis, and protein translation, and has been shown to have prognostic significance in a number of cancers. We sought to define its role in extrahepatic cholangiocarcinoma. Experimental Design: Tw...
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| Veröffentlicht in: | Clinical cancer research 2009-01, Vol.15 (2), p.660-667 |
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| creator | Chung, Joon-Yong Hong, Seung-Mo Choi, Byeong Yeob Cho, Hyungjun Yu, Eunsil Hewitt, Stephen M |
| description | Purpose: The protein kinase B (AKT) pathway plays a key role in the regulation of cellular survival, apoptosis, and protein translation,
and has been shown to have prognostic significance in a number of cancers. We sought to define its role in extrahepatic cholangiocarcinoma.
Experimental Design: Two hundred twenty-one extrahepatic cholangiocarcinoma patients with clinicopathologic data, including survival, were arrayed
into tissue microarrays. Phosphorylated AKT (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and total phosphatase
and tensin homolog deleted on chromosome 10 (PTEN) protein expressions were studied with multiplex tissue immunoblotting assay.
Results: Expressions of p-AKT and p-mTOR were significantly increased in extrahepatic cholangiocarcinoma cases compared with normal
and dysplastic bile duct epithelium ( P < 0.05 both). Decreased PTEN expression was observed in patients with increasing depth of invasion ( P < 0.05), T classification ( P < 0.05), and stage grouping ( P < 0.05), and the presence of invasion of the pancreas ( P < 0.05) and duodenum ( P < 0.05). Decreased PTEN expression ( P = 0.004) as well as decreased PTEN/p-AKT ( P = 0.003) and PTEN/p-mTOR ( P = 0.009) expression showed shorter survival by univariate but not by multivariate analysis.
Conclusions: The AKT pathway is activated in a subset of extrahepatic cholangiocarcinoma. Elevated PTEN expression correlates with longer
survival. Quantitative data obtained by multiplex tissue immunoblotting may provide additional information than assessment
of immunohistochemistry alone. Quantitative analysis of PTEN, PTEN/p-AKT and PTEN/p-mTOR shows differences in survival by
univariate analysis. |
| doi_str_mv | 10.1158/1078-0432.CCR-08-1084 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7556734</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>66825271</sourcerecordid><originalsourceid>FETCH-LOGICAL-c537t-7cbaebcd93cd9c90c270fba436a7f50f2716afcb432daa8bee22d68488c5edb03</originalsourceid><addsrcrecordid>eNpVkdtu1DAQhi1URA_wCFS5Kb1pig9x7L1BqqItICpaVUHizpo4ztpVEqf2bgtvX0e7LHBh-fTNzD_zI_Se4EtCuPxIsJA5Lhi9rKr7HMucYFm8QkeEc5EzWvKDdP7DHKLjGB8wJgXBxRt0SBakEELQI_SztiZb_pqCidH5MfNddmd9nKzPr77VF_vLUN_eX2QwttldvfyeuTEFrQNYM8Ha6ayyvodx5byGoN3oB3iLXnfQR_Nut5-gH9fLuvqS39x-_lpd3eSaM7HOhW7ANLpdsLT0AmsqcNdAwUoQHccdFaSETjepiRZANsZQ2paykFJz0zaYnaBP27zTphlMq82YZPVqCm6A8Ft5cOr_n9FZtfJPSnBeClakBB92CYJ_3Ji4VoOL2vSpH-M3UZWlpDzJSCDfgjr4GIPp9kUIVrMnap63muetkicKzw9yLnD6r8K_UTsTEnC2AyBq6LsAo3Zxz1HC2WKr9HzLWbeyzy4YpRNpQvLOpLFbRbiiSS9mL_GLpEc</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>66825271</pqid></control><display><type>article</type><title>The Expression of Phospho-AKT, Phospho-mTOR, and PTEN in Extrahepatic Cholangiocarcinoma</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Chung, Joon-Yong ; Hong, Seung-Mo ; Choi, Byeong Yeob ; Cho, Hyungjun ; Yu, Eunsil ; Hewitt, Stephen M</creator><creatorcontrib>Chung, Joon-Yong ; Hong, Seung-Mo ; Choi, Byeong Yeob ; Cho, Hyungjun ; Yu, Eunsil ; Hewitt, Stephen M</creatorcontrib><description><![CDATA[Purpose: The protein kinase B (AKT) pathway plays a key role in the regulation of cellular survival, apoptosis, and protein translation,
and has been shown to have prognostic significance in a number of cancers. We sought to define its role in extrahepatic cholangiocarcinoma.
Experimental Design: Two hundred twenty-one extrahepatic cholangiocarcinoma patients with clinicopathologic data, including survival, were arrayed
into tissue microarrays. Phosphorylated AKT (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and total phosphatase
and tensin homolog deleted on chromosome 10 (PTEN) protein expressions were studied with multiplex tissue immunoblotting assay.
Results: Expressions of p-AKT and p-mTOR were significantly increased in extrahepatic cholangiocarcinoma cases compared with normal
and dysplastic bile duct epithelium ( P < 0.05 both). Decreased PTEN expression was observed in patients with increasing depth of invasion ( P < 0.05), T classification ( P < 0.05), and stage grouping ( P < 0.05), and the presence of invasion of the pancreas ( P < 0.05) and duodenum ( P < 0.05). Decreased PTEN expression ( P = 0.004) as well as decreased PTEN/p-AKT ( P = 0.003) and PTEN/p-mTOR ( P = 0.009) expression showed shorter survival by univariate but not by multivariate analysis.
Conclusions: The AKT pathway is activated in a subset of extrahepatic cholangiocarcinoma. Elevated PTEN expression correlates with longer
survival. Quantitative data obtained by multiplex tissue immunoblotting may provide additional information than assessment
of immunohistochemistry alone. Quantitative analysis of PTEN, PTEN/p-AKT and PTEN/p-mTOR shows differences in survival by
univariate analysis.]]></description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-08-1084</identifier><identifier>PMID: 19147772</identifier><identifier>CODEN: CCREF4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Aged ; AKT ; Antineoplastic agents ; Apoptosis ; Biological and medical sciences ; Cholangiocarcinoma - metabolism ; extrahepatic cholangiocarcinoma ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression Regulation, Neoplastic ; Humans ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Middle Aged ; mTOR ; Neoplasms - metabolism ; Oligonucleotide Array Sequence Analysis ; Pharmacology. Drug treatments ; Phosphorylation ; Protein Kinases - biosynthesis ; Protein Kinases - physiology ; proteomics ; Proteomics - methods ; Proto-Oncogene Proteins c-akt - biosynthesis ; Proto-Oncogene Proteins c-akt - physiology ; PTEN ; PTEN Phosphohydrolase - biosynthesis ; PTEN Phosphohydrolase - metabolism ; PTEN Phosphohydrolase - physiology ; TOR Serine-Threonine Kinases ; Tumors</subject><ispartof>Clinical cancer research, 2009-01, Vol.15 (2), p.660-667</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c537t-7cbaebcd93cd9c90c270fba436a7f50f2716afcb432daa8bee22d68488c5edb03</citedby><cites>FETCH-LOGICAL-c537t-7cbaebcd93cd9c90c270fba436a7f50f2716afcb432daa8bee22d68488c5edb03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3356,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21539734$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19147772$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chung, Joon-Yong</creatorcontrib><creatorcontrib>Hong, Seung-Mo</creatorcontrib><creatorcontrib>Choi, Byeong Yeob</creatorcontrib><creatorcontrib>Cho, Hyungjun</creatorcontrib><creatorcontrib>Yu, Eunsil</creatorcontrib><creatorcontrib>Hewitt, Stephen M</creatorcontrib><title>The Expression of Phospho-AKT, Phospho-mTOR, and PTEN in Extrahepatic Cholangiocarcinoma</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description><![CDATA[Purpose: The protein kinase B (AKT) pathway plays a key role in the regulation of cellular survival, apoptosis, and protein translation,
and has been shown to have prognostic significance in a number of cancers. We sought to define its role in extrahepatic cholangiocarcinoma.
Experimental Design: Two hundred twenty-one extrahepatic cholangiocarcinoma patients with clinicopathologic data, including survival, were arrayed
into tissue microarrays. Phosphorylated AKT (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and total phosphatase
and tensin homolog deleted on chromosome 10 (PTEN) protein expressions were studied with multiplex tissue immunoblotting assay.
Results: Expressions of p-AKT and p-mTOR were significantly increased in extrahepatic cholangiocarcinoma cases compared with normal
and dysplastic bile duct epithelium ( P < 0.05 both). Decreased PTEN expression was observed in patients with increasing depth of invasion ( P < 0.05), T classification ( P < 0.05), and stage grouping ( P < 0.05), and the presence of invasion of the pancreas ( P < 0.05) and duodenum ( P < 0.05). Decreased PTEN expression ( P = 0.004) as well as decreased PTEN/p-AKT ( P = 0.003) and PTEN/p-mTOR ( P = 0.009) expression showed shorter survival by univariate but not by multivariate analysis.
Conclusions: The AKT pathway is activated in a subset of extrahepatic cholangiocarcinoma. Elevated PTEN expression correlates with longer
survival. Quantitative data obtained by multiplex tissue immunoblotting may provide additional information than assessment
of immunohistochemistry alone. Quantitative analysis of PTEN, PTEN/p-AKT and PTEN/p-mTOR shows differences in survival by
univariate analysis.]]></description><subject>Aged</subject><subject>AKT</subject><subject>Antineoplastic agents</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Cholangiocarcinoma - metabolism</subject><subject>extrahepatic cholangiocarcinoma</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>mTOR</subject><subject>Neoplasms - metabolism</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphorylation</subject><subject>Protein Kinases - biosynthesis</subject><subject>Protein Kinases - physiology</subject><subject>proteomics</subject><subject>Proteomics - methods</subject><subject>Proto-Oncogene Proteins c-akt - biosynthesis</subject><subject>Proto-Oncogene Proteins c-akt - physiology</subject><subject>PTEN</subject><subject>PTEN Phosphohydrolase - biosynthesis</subject><subject>PTEN Phosphohydrolase - metabolism</subject><subject>PTEN Phosphohydrolase - physiology</subject><subject>TOR Serine-Threonine Kinases</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkdtu1DAQhi1URA_wCFS5Kb1pig9x7L1BqqItICpaVUHizpo4ztpVEqf2bgtvX0e7LHBh-fTNzD_zI_Se4EtCuPxIsJA5Lhi9rKr7HMucYFm8QkeEc5EzWvKDdP7DHKLjGB8wJgXBxRt0SBakEELQI_SztiZb_pqCidH5MfNddmd9nKzPr77VF_vLUN_eX2QwttldvfyeuTEFrQNYM8Ha6ayyvodx5byGoN3oB3iLXnfQR_Nut5-gH9fLuvqS39x-_lpd3eSaM7HOhW7ANLpdsLT0AmsqcNdAwUoQHccdFaSETjepiRZANsZQ2paykFJz0zaYnaBP27zTphlMq82YZPVqCm6A8Ft5cOr_n9FZtfJPSnBeClakBB92CYJ_3Ji4VoOL2vSpH-M3UZWlpDzJSCDfgjr4GIPp9kUIVrMnap63muetkicKzw9yLnD6r8K_UTsTEnC2AyBq6LsAo3Zxz1HC2WKr9HzLWbeyzy4YpRNpQvLOpLFbRbiiSS9mL_GLpEc</recordid><startdate>20090115</startdate><enddate>20090115</enddate><creator>Chung, Joon-Yong</creator><creator>Hong, Seung-Mo</creator><creator>Choi, Byeong Yeob</creator><creator>Cho, Hyungjun</creator><creator>Yu, Eunsil</creator><creator>Hewitt, Stephen M</creator><general>American Association for Cancer Research</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><scope>5PM</scope></search><sort><creationdate>20090115</creationdate><title>The Expression of Phospho-AKT, Phospho-mTOR, and PTEN in Extrahepatic Cholangiocarcinoma</title><author>Chung, Joon-Yong ; Hong, Seung-Mo ; Choi, Byeong Yeob ; Cho, Hyungjun ; Yu, Eunsil ; Hewitt, Stephen M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c537t-7cbaebcd93cd9c90c270fba436a7f50f2716afcb432daa8bee22d68488c5edb03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Aged</topic><topic>AKT</topic><topic>Antineoplastic agents</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Cholangiocarcinoma - metabolism</topic><topic>extrahepatic cholangiocarcinoma</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>mTOR</topic><topic>Neoplasms - metabolism</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphorylation</topic><topic>Protein Kinases - biosynthesis</topic><topic>Protein Kinases - physiology</topic><topic>proteomics</topic><topic>Proteomics - methods</topic><topic>Proto-Oncogene Proteins c-akt - biosynthesis</topic><topic>Proto-Oncogene Proteins c-akt - physiology</topic><topic>PTEN</topic><topic>PTEN Phosphohydrolase - biosynthesis</topic><topic>PTEN Phosphohydrolase - metabolism</topic><topic>PTEN Phosphohydrolase - physiology</topic><topic>TOR Serine-Threonine Kinases</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chung, Joon-Yong</creatorcontrib><creatorcontrib>Hong, Seung-Mo</creatorcontrib><creatorcontrib>Choi, Byeong Yeob</creatorcontrib><creatorcontrib>Cho, Hyungjun</creatorcontrib><creatorcontrib>Yu, Eunsil</creatorcontrib><creatorcontrib>Hewitt, Stephen M</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chung, Joon-Yong</au><au>Hong, Seung-Mo</au><au>Choi, Byeong Yeob</au><au>Cho, Hyungjun</au><au>Yu, Eunsil</au><au>Hewitt, Stephen M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Expression of Phospho-AKT, Phospho-mTOR, and PTEN in Extrahepatic Cholangiocarcinoma</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2009-01-15</date><risdate>2009</risdate><volume>15</volume><issue>2</issue><spage>660</spage><epage>667</epage><pages>660-667</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><coden>CCREF4</coden><abstract><![CDATA[Purpose: The protein kinase B (AKT) pathway plays a key role in the regulation of cellular survival, apoptosis, and protein translation,
and has been shown to have prognostic significance in a number of cancers. We sought to define its role in extrahepatic cholangiocarcinoma.
Experimental Design: Two hundred twenty-one extrahepatic cholangiocarcinoma patients with clinicopathologic data, including survival, were arrayed
into tissue microarrays. Phosphorylated AKT (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and total phosphatase
and tensin homolog deleted on chromosome 10 (PTEN) protein expressions were studied with multiplex tissue immunoblotting assay.
Results: Expressions of p-AKT and p-mTOR were significantly increased in extrahepatic cholangiocarcinoma cases compared with normal
and dysplastic bile duct epithelium ( P < 0.05 both). Decreased PTEN expression was observed in patients with increasing depth of invasion ( P < 0.05), T classification ( P < 0.05), and stage grouping ( P < 0.05), and the presence of invasion of the pancreas ( P < 0.05) and duodenum ( P < 0.05). Decreased PTEN expression ( P = 0.004) as well as decreased PTEN/p-AKT ( P = 0.003) and PTEN/p-mTOR ( P = 0.009) expression showed shorter survival by univariate but not by multivariate analysis.
Conclusions: The AKT pathway is activated in a subset of extrahepatic cholangiocarcinoma. Elevated PTEN expression correlates with longer
survival. Quantitative data obtained by multiplex tissue immunoblotting may provide additional information than assessment
of immunohistochemistry alone. Quantitative analysis of PTEN, PTEN/p-AKT and PTEN/p-mTOR shows differences in survival by
univariate analysis.]]></abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>19147772</pmid><doi>10.1158/1078-0432.CCR-08-1084</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Aged AKT Antineoplastic agents Apoptosis Biological and medical sciences Cholangiocarcinoma - metabolism extrahepatic cholangiocarcinoma Female Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Regulation, Neoplastic Humans Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Middle Aged mTOR Neoplasms - metabolism Oligonucleotide Array Sequence Analysis Pharmacology. Drug treatments Phosphorylation Protein Kinases - biosynthesis Protein Kinases - physiology proteomics Proteomics - methods Proto-Oncogene Proteins c-akt - biosynthesis Proto-Oncogene Proteins c-akt - physiology PTEN PTEN Phosphohydrolase - biosynthesis PTEN Phosphohydrolase - metabolism PTEN Phosphohydrolase - physiology TOR Serine-Threonine Kinases Tumors |
| title | The Expression of Phospho-AKT, Phospho-mTOR, and PTEN in Extrahepatic Cholangiocarcinoma |
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