Increased NBS1 Expression Is a Marker of Aggressive Head and Neck Cancer and Overexpression of NBS1 Contributes to Transformation
Purpose: Head and neck squamous cell carcinoma (HNSCC) represents the sixth most frequent type of cancer worldwide. However, the molecular genetic alterations underlying its malignant behavior and progression are little known. We showed previously that c-MYC directly activates the expression of the...
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| Veröffentlicht in: | Clinical cancer research 2006-01, Vol.12 (2), p.507-515 |
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| creator | YANG, Muh-Hwa CHIANG, Wei-Chung CHOU, Teh-Ying CHANG, Shyue-Yih CHEN, Po-Min TENG, Shu-Chun WU, Kou-Juey |
| description | Purpose: Head and neck squamous cell carcinoma (HNSCC) represents the sixth most frequent type of cancer worldwide. However, the molecular
genetic alterations underlying its malignant behavior and progression are little known. We showed previously that c-MYC directly
activates the expression of the DNA double-strand break repair gene NBS1 , and NBS1 overexpression contributes to transformation. Here, we investigate the role of NBS1 overexpression in HNSCC.
Experimental Design: Immunohistochemistry analysis of NBS1 expression was done in 81 locally advanced HNSCC patients. Real-time PCR and Western
blot analysis were used to confirm immunohistochemistry results. Human hypopharyngeal cancer cell lines (FADU) with overexpressing
NBS1 (FADUNBS) or inducible short interference RNA to repress endogenous NBS1 (FADUNBSi) were generated by stable transfection.
Soft agar clonogenicity assay was used to determine the transformation activity. Western blot analysis and phosphatidylinositol
3-kinase (PI3K) assay were done to evaluate the signaling pathways that were involved.
Results: NBS1 overexpression was identified in 45% of advanced HNSCC patients. It was an independent marker of poor prognosis. NBS1
expression levels correlated with the transformation activity of FADU clones and also correlated with the phosphorylation
levels of Akt and its downstream target mammalian target of rapamycin (mTOR). PI3K activity was increased in NBS1-overexpressing
FADU clones. NBS1 overexpression also correlated with increased Akt phosphorylation levels in tumor samples.
Conclusions: Increased NBS1 expression is a significant prognostic marker of advanced HNSCC, and the underlying mechanism may involve
the activation of the PI3K/Akt pathway. |
| doi_str_mv | 10.1158/1078-0432.CCR-05-1231 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70695564</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17466354</sourcerecordid><originalsourceid>FETCH-LOGICAL-c466t-360bf25191e3dc440c1d520a7f5a22f8599fceadff61207ae9360ceb8a7633313</originalsourceid><addsrcrecordid>eNqFkcFuEzEQhlcIREvhEUC-AKdtPbbH3j2WVaGRSitBOVuOd5wsTXaDvSlw5M3xJkE5crItf__MaL6ieA38HACrC-CmKrmS4rxpvpQcSxASnhSngGhKKTQ-zfd_zEnxIqXvnIMCrp4XJ6CVqFQtT4s_s95HcoladvvhK7CrX5tIKXVDz2aJOfbZxQeKbAjscrHY_TwSuybXMtfnCPkH1rjeZ2R63z1SpGOFnNoVbYZ-jN18O1Ji48Duo-tTGOLajZl6WTwLbpXo1eE8K759vLpvrsubu0-z5vKm9ErrsZSaz4NAqIFk65XiHloU3JmATohQYV0Hn-cKQYPgxlGdE57mlTNaSgnyrHi3r7uJw48tpdGuu-RptXI9DdtkDdc1olb_BcHkgSROIO5BH4eUIgW7id3axd8WuJ0k2UmAnQTYLMlytJOknHtzaLCdr6k9pg5WMvD2ALjk3SrkffkuHTmDgKrGzL3fc8tusfzZRbJ-5yLvn1z0y9zOCovcyL9hPae5</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17466354</pqid></control><display><type>article</type><title>Increased NBS1 Expression Is a Marker of Aggressive Head and Neck Cancer and Overexpression of NBS1 Contributes to Transformation</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>YANG, Muh-Hwa ; CHIANG, Wei-Chung ; CHOU, Teh-Ying ; CHANG, Shyue-Yih ; CHEN, Po-Min ; TENG, Shu-Chun ; WU, Kou-Juey</creator><creatorcontrib>YANG, Muh-Hwa ; CHIANG, Wei-Chung ; CHOU, Teh-Ying ; CHANG, Shyue-Yih ; CHEN, Po-Min ; TENG, Shu-Chun ; WU, Kou-Juey</creatorcontrib><description>Purpose: Head and neck squamous cell carcinoma (HNSCC) represents the sixth most frequent type of cancer worldwide. However, the molecular
genetic alterations underlying its malignant behavior and progression are little known. We showed previously that c-MYC directly
activates the expression of the DNA double-strand break repair gene NBS1 , and NBS1 overexpression contributes to transformation. Here, we investigate the role of NBS1 overexpression in HNSCC.
Experimental Design: Immunohistochemistry analysis of NBS1 expression was done in 81 locally advanced HNSCC patients. Real-time PCR and Western
blot analysis were used to confirm immunohistochemistry results. Human hypopharyngeal cancer cell lines (FADU) with overexpressing
NBS1 (FADUNBS) or inducible short interference RNA to repress endogenous NBS1 (FADUNBSi) were generated by stable transfection.
Soft agar clonogenicity assay was used to determine the transformation activity. Western blot analysis and phosphatidylinositol
3-kinase (PI3K) assay were done to evaluate the signaling pathways that were involved.
Results: NBS1 overexpression was identified in 45% of advanced HNSCC patients. It was an independent marker of poor prognosis. NBS1
expression levels correlated with the transformation activity of FADU clones and also correlated with the phosphorylation
levels of Akt and its downstream target mammalian target of rapamycin (mTOR). PI3K activity was increased in NBS1-overexpressing
FADU clones. NBS1 overexpression also correlated with increased Akt phosphorylation levels in tumor samples.
Conclusions: Increased NBS1 expression is a significant prognostic marker of advanced HNSCC, and the underlying mechanism may involve
the activation of the PI3K/Akt pathway.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-05-1231</identifier><identifier>PMID: 16428493</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Akt ; Antineoplastic agents ; Biological and medical sciences ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Blotting, Western ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell Cycle Proteins - antagonists & inhibitors ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Cell Transformation, Neoplastic ; Class I Phosphatidylinositol 3-Kinases ; Female ; head and neck cancer ; Head and Neck Neoplasms - genetics ; Head and Neck Neoplasms - metabolism ; Head and Neck Neoplasms - pathology ; Humans ; Male ; Medical sciences ; Middle Aged ; NBS1 ; Nuclear Proteins - antagonists & inhibitors ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Otorhinolaryngology (head neck, general aspects and miscellaneous) ; Otorhinolaryngology. Stomatology ; Pharmacology. Drug treatments ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation ; prognosis ; Proto-Oncogene Proteins c-akt - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Small Interfering - pharmacology ; Signal Transduction ; transformation ; Tumor Cells, Cultured ; Tumors</subject><ispartof>Clinical cancer research, 2006-01, Vol.12 (2), p.507-515</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c466t-360bf25191e3dc440c1d520a7f5a22f8599fceadff61207ae9360ceb8a7633313</citedby><cites>FETCH-LOGICAL-c466t-360bf25191e3dc440c1d520a7f5a22f8599fceadff61207ae9360ceb8a7633313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3355,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17515495$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16428493$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>YANG, Muh-Hwa</creatorcontrib><creatorcontrib>CHIANG, Wei-Chung</creatorcontrib><creatorcontrib>CHOU, Teh-Ying</creatorcontrib><creatorcontrib>CHANG, Shyue-Yih</creatorcontrib><creatorcontrib>CHEN, Po-Min</creatorcontrib><creatorcontrib>TENG, Shu-Chun</creatorcontrib><creatorcontrib>WU, Kou-Juey</creatorcontrib><title>Increased NBS1 Expression Is a Marker of Aggressive Head and Neck Cancer and Overexpression of NBS1 Contributes to Transformation</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: Head and neck squamous cell carcinoma (HNSCC) represents the sixth most frequent type of cancer worldwide. However, the molecular
genetic alterations underlying its malignant behavior and progression are little known. We showed previously that c-MYC directly
activates the expression of the DNA double-strand break repair gene NBS1 , and NBS1 overexpression contributes to transformation. Here, we investigate the role of NBS1 overexpression in HNSCC.
Experimental Design: Immunohistochemistry analysis of NBS1 expression was done in 81 locally advanced HNSCC patients. Real-time PCR and Western
blot analysis were used to confirm immunohistochemistry results. Human hypopharyngeal cancer cell lines (FADU) with overexpressing
NBS1 (FADUNBS) or inducible short interference RNA to repress endogenous NBS1 (FADUNBSi) were generated by stable transfection.
Soft agar clonogenicity assay was used to determine the transformation activity. Western blot analysis and phosphatidylinositol
3-kinase (PI3K) assay were done to evaluate the signaling pathways that were involved.
Results: NBS1 overexpression was identified in 45% of advanced HNSCC patients. It was an independent marker of poor prognosis. NBS1
expression levels correlated with the transformation activity of FADU clones and also correlated with the phosphorylation
levels of Akt and its downstream target mammalian target of rapamycin (mTOR). PI3K activity was increased in NBS1-overexpressing
FADU clones. NBS1 overexpression also correlated with increased Akt phosphorylation levels in tumor samples.
Conclusions: Increased NBS1 expression is a significant prognostic marker of advanced HNSCC, and the underlying mechanism may involve
the activation of the PI3K/Akt pathway.</description><subject>Adult</subject><subject>Aged</subject><subject>Akt</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Blotting, Western</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell Cycle Proteins - antagonists & inhibitors</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Transformation, Neoplastic</subject><subject>Class I Phosphatidylinositol 3-Kinases</subject><subject>Female</subject><subject>head and neck cancer</subject><subject>Head and Neck Neoplasms - genetics</subject><subject>Head and Neck Neoplasms - metabolism</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>NBS1</subject><subject>Nuclear Proteins - antagonists & inhibitors</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Otorhinolaryngology (head neck, general aspects and miscellaneous)</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>prognosis</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>Signal Transduction</subject><subject>transformation</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFuEzEQhlcIREvhEUC-AKdtPbbH3j2WVaGRSitBOVuOd5wsTXaDvSlw5M3xJkE5crItf__MaL6ieA38HACrC-CmKrmS4rxpvpQcSxASnhSngGhKKTQ-zfd_zEnxIqXvnIMCrp4XJ6CVqFQtT4s_s95HcoladvvhK7CrX5tIKXVDz2aJOfbZxQeKbAjscrHY_TwSuybXMtfnCPkH1rjeZ2R63z1SpGOFnNoVbYZ-jN18O1Ji48Duo-tTGOLajZl6WTwLbpXo1eE8K759vLpvrsubu0-z5vKm9ErrsZSaz4NAqIFk65XiHloU3JmATohQYV0Hn-cKQYPgxlGdE57mlTNaSgnyrHi3r7uJw48tpdGuu-RptXI9DdtkDdc1olb_BcHkgSROIO5BH4eUIgW7id3axd8WuJ0k2UmAnQTYLMlytJOknHtzaLCdr6k9pg5WMvD2ALjk3SrkffkuHTmDgKrGzL3fc8tusfzZRbJ-5yLvn1z0y9zOCovcyL9hPae5</recordid><startdate>20060115</startdate><enddate>20060115</enddate><creator>YANG, Muh-Hwa</creator><creator>CHIANG, Wei-Chung</creator><creator>CHOU, Teh-Ying</creator><creator>CHANG, Shyue-Yih</creator><creator>CHEN, Po-Min</creator><creator>TENG, Shu-Chun</creator><creator>WU, Kou-Juey</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>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20060115</creationdate><title>Increased NBS1 Expression Is a Marker of Aggressive Head and Neck Cancer and Overexpression of NBS1 Contributes to Transformation</title><author>YANG, Muh-Hwa ; CHIANG, Wei-Chung ; CHOU, Teh-Ying ; CHANG, Shyue-Yih ; CHEN, Po-Min ; TENG, Shu-Chun ; WU, Kou-Juey</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c466t-360bf25191e3dc440c1d520a7f5a22f8599fceadff61207ae9360ceb8a7633313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Akt</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Blotting, Western</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cell Cycle Proteins - antagonists & inhibitors</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Transformation, Neoplastic</topic><topic>Class I Phosphatidylinositol 3-Kinases</topic><topic>Female</topic><topic>head and neck cancer</topic><topic>Head and Neck Neoplasms - genetics</topic><topic>Head and Neck Neoplasms - metabolism</topic><topic>Head and Neck Neoplasms - pathology</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>NBS1</topic><topic>Nuclear Proteins - antagonists & inhibitors</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Otorhinolaryngology (head neck, general aspects and miscellaneous)</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphorylation</topic><topic>prognosis</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>Signal Transduction</topic><topic>transformation</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>YANG, Muh-Hwa</creatorcontrib><creatorcontrib>CHIANG, Wei-Chung</creatorcontrib><creatorcontrib>CHOU, Teh-Ying</creatorcontrib><creatorcontrib>CHANG, Shyue-Yih</creatorcontrib><creatorcontrib>CHEN, Po-Min</creatorcontrib><creatorcontrib>TENG, Shu-Chun</creatorcontrib><creatorcontrib>WU, Kou-Juey</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>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>YANG, Muh-Hwa</au><au>CHIANG, Wei-Chung</au><au>CHOU, Teh-Ying</au><au>CHANG, Shyue-Yih</au><au>CHEN, Po-Min</au><au>TENG, Shu-Chun</au><au>WU, Kou-Juey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased NBS1 Expression Is a Marker of Aggressive Head and Neck Cancer and Overexpression of NBS1 Contributes to Transformation</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2006-01-15</date><risdate>2006</risdate><volume>12</volume><issue>2</issue><spage>507</spage><epage>515</epage><pages>507-515</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: Head and neck squamous cell carcinoma (HNSCC) represents the sixth most frequent type of cancer worldwide. However, the molecular
genetic alterations underlying its malignant behavior and progression are little known. We showed previously that c-MYC directly
activates the expression of the DNA double-strand break repair gene NBS1 , and NBS1 overexpression contributes to transformation. Here, we investigate the role of NBS1 overexpression in HNSCC.
Experimental Design: Immunohistochemistry analysis of NBS1 expression was done in 81 locally advanced HNSCC patients. Real-time PCR and Western
blot analysis were used to confirm immunohistochemistry results. Human hypopharyngeal cancer cell lines (FADU) with overexpressing
NBS1 (FADUNBS) or inducible short interference RNA to repress endogenous NBS1 (FADUNBSi) were generated by stable transfection.
Soft agar clonogenicity assay was used to determine the transformation activity. Western blot analysis and phosphatidylinositol
3-kinase (PI3K) assay were done to evaluate the signaling pathways that were involved.
Results: NBS1 overexpression was identified in 45% of advanced HNSCC patients. It was an independent marker of poor prognosis. NBS1
expression levels correlated with the transformation activity of FADU clones and also correlated with the phosphorylation
levels of Akt and its downstream target mammalian target of rapamycin (mTOR). PI3K activity was increased in NBS1-overexpressing
FADU clones. NBS1 overexpression also correlated with increased Akt phosphorylation levels in tumor samples.
Conclusions: Increased NBS1 expression is a significant prognostic marker of advanced HNSCC, and the underlying mechanism may involve
the activation of the PI3K/Akt pathway.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>16428493</pmid><doi>10.1158/1078-0432.CCR-05-1231</doi><tpages>9</tpages></addata></record> |
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| ispartof | Clinical cancer research, 2006-01, Vol.12 (2), p.507-515 |
| issn | 1078-0432 1557-3265 |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Aged Akt Antineoplastic agents Biological and medical sciences Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Blotting, Western Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Cell Cycle Proteins - antagonists & inhibitors Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Transformation, Neoplastic Class I Phosphatidylinositol 3-Kinases Female head and neck cancer Head and Neck Neoplasms - genetics Head and Neck Neoplasms - metabolism Head and Neck Neoplasms - pathology Humans Male Medical sciences Middle Aged NBS1 Nuclear Proteins - antagonists & inhibitors Nuclear Proteins - genetics Nuclear Proteins - metabolism Otorhinolaryngology (head neck, general aspects and miscellaneous) Otorhinolaryngology. Stomatology Pharmacology. Drug treatments Phosphatidylinositol 3-Kinases - metabolism Phosphorylation prognosis Proto-Oncogene Proteins c-akt - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Small Interfering - pharmacology Signal Transduction transformation Tumor Cells, Cultured Tumors |
| title | Increased NBS1 Expression Is a Marker of Aggressive Head and Neck Cancer and Overexpression of NBS1 Contributes to Transformation |
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