p73-dependent induction of 14-3-3sigma increases the chemo-sensitivity of drug-resistant human breast cancers
It has been well documented that tumor suppressor p53 is mutated in about 50% of all human tumors. p53 status might be one of the critical determinants for the chemo-sensitivity of human tumors. In the present study, we have found that p53 family member p73 as well as 14-3-3sigma is down-regulated i...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2006-08, Vol.347 (1), p.327-333 |
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| creator | Sang, Meixiang Li, Yuanyuan Ozaki, Toshinori Ono, Sayaka Ando, Kiyohiro Yamamoto, Hideki Koda, Tadayuki Geng, Cuizhi Nakagawara, Akira |
| description | It has been well documented that tumor suppressor p53 is mutated in about 50% of all human tumors. p53 status might be one of the critical determinants for the chemo-sensitivity of human tumors. In the present study, we have found that p53 family member p73 as well as 14-3-3sigma is down-regulated in response to adriamycin (ADR) in ADR-resistant human breast cancer-derived MBA-MD-436 cells which carry p53 mutation. Like p53, 14-3-3sigma was transactivated by p73 and, in turn, stabilized p73. Luciferase reporter analysis and colony formation assays demonstrated that 14-3-3sigma has an ability to enhance the p73-mediated transcriptional activity as well as its pro-apoptotic function. Furthermore, enforced expression of 14-3-3sigma increased the ADR sensitivity of MBA-MD-436 cells. Taken together, our present results strongly suggest that p73-dependent induction of 14-3-3sigma plays an important role in the regulation of chemo-sensitivity of breast cancers bearing p53 mutation. |
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In the present study, we have found that p53 family member p73 as well as 14-3-3sigma is down-regulated in response to adriamycin (ADR) in ADR-resistant human breast cancer-derived MBA-MD-436 cells which carry p53 mutation. Like p53, 14-3-3sigma was transactivated by p73 and, in turn, stabilized p73. Luciferase reporter analysis and colony formation assays demonstrated that 14-3-3sigma has an ability to enhance the p73-mediated transcriptional activity as well as its pro-apoptotic function. Furthermore, enforced expression of 14-3-3sigma increased the ADR sensitivity of MBA-MD-436 cells. Taken together, our present results strongly suggest that p73-dependent induction of 14-3-3sigma plays an important role in the regulation of chemo-sensitivity of breast cancers bearing p53 mutation.</description><identifier>ISSN: 0006-291X</identifier><identifier>PMID: 16814250</identifier><language>eng</language><publisher>United States</publisher><subject>14-3-3 Proteins ; Antibiotics, Antineoplastic - administration & dosage ; Biomarkers, Tumor ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cell Line, Tumor ; Cell Survival - drug effects ; DNA-Binding Proteins - metabolism ; Dose-Response Relationship, Drug ; Doxorubicin - administration & dosage ; Drug Resistance, Neoplasm ; Exonucleases ; Exoribonucleases ; Gene Expression Regulation, Neoplastic - drug effects ; Genes, Tumor Suppressor ; Humans ; Neoplasm Proteins ; Nuclear Proteins - metabolism ; Tumor Protein p73 ; Tumor Suppressor Protein p53 - metabolism ; Tumor Suppressor Proteins</subject><ispartof>Biochemical and biophysical research communications, 2006-08, Vol.347 (1), p.327-333</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16814250$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sang, Meixiang</creatorcontrib><creatorcontrib>Li, Yuanyuan</creatorcontrib><creatorcontrib>Ozaki, Toshinori</creatorcontrib><creatorcontrib>Ono, Sayaka</creatorcontrib><creatorcontrib>Ando, Kiyohiro</creatorcontrib><creatorcontrib>Yamamoto, Hideki</creatorcontrib><creatorcontrib>Koda, Tadayuki</creatorcontrib><creatorcontrib>Geng, Cuizhi</creatorcontrib><creatorcontrib>Nakagawara, Akira</creatorcontrib><title>p73-dependent induction of 14-3-3sigma increases the chemo-sensitivity of drug-resistant human breast cancers</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>It has been well documented that tumor suppressor p53 is mutated in about 50% of all human tumors. p53 status might be one of the critical determinants for the chemo-sensitivity of human tumors. In the present study, we have found that p53 family member p73 as well as 14-3-3sigma is down-regulated in response to adriamycin (ADR) in ADR-resistant human breast cancer-derived MBA-MD-436 cells which carry p53 mutation. Like p53, 14-3-3sigma was transactivated by p73 and, in turn, stabilized p73. Luciferase reporter analysis and colony formation assays demonstrated that 14-3-3sigma has an ability to enhance the p73-mediated transcriptional activity as well as its pro-apoptotic function. Furthermore, enforced expression of 14-3-3sigma increased the ADR sensitivity of MBA-MD-436 cells. Taken together, our present results strongly suggest that p73-dependent induction of 14-3-3sigma plays an important role in the regulation of chemo-sensitivity of breast cancers bearing p53 mutation.</description><subject>14-3-3 Proteins</subject><subject>Antibiotics, Antineoplastic - administration & dosage</subject><subject>Biomarkers, Tumor</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Doxorubicin - administration & dosage</subject><subject>Drug Resistance, Neoplasm</subject><subject>Exonucleases</subject><subject>Exoribonucleases</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Genes, Tumor Suppressor</subject><subject>Humans</subject><subject>Neoplasm Proteins</subject><subject>Nuclear Proteins - metabolism</subject><subject>Tumor Protein p73</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumor Suppressor Proteins</subject><issn>0006-291X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kD1PwzAYhD2AaCn8BeSJzZK_k4yo4kuqxNKBLXLsN41R7QTbQeq_JxVlupPuuRvuCq0ppZrwhn2u0G3OX5QyJnVzg1ZM10xyRdcoTJUgDiaIDmLBPrrZFj9GPPaYSSKIyP4QzBLYBCZDxmUAbAcII8kQsy_-x5fTGXdpPpAE2edilqlhDibi7twq2JpoIeU7dN2bY4b7i27Q_uV5v30ju4_X9-3TjkxKUsLAGFGBNoxp21VG646LntWG2sU6xZmrK6m07C2nTLPaNl0jeqk7qhxoLjbo8W92SuP3DLm0wWcLx6OJMM651bXmqhFqAR8u4NwFcO2UfDDp1P7_I34B7_hhDQ</recordid><startdate>20060818</startdate><enddate>20060818</enddate><creator>Sang, Meixiang</creator><creator>Li, Yuanyuan</creator><creator>Ozaki, Toshinori</creator><creator>Ono, Sayaka</creator><creator>Ando, Kiyohiro</creator><creator>Yamamoto, Hideki</creator><creator>Koda, Tadayuki</creator><creator>Geng, Cuizhi</creator><creator>Nakagawara, Akira</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20060818</creationdate><title>p73-dependent induction of 14-3-3sigma increases the chemo-sensitivity of drug-resistant human breast cancers</title><author>Sang, Meixiang ; 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| subjects | 14-3-3 Proteins Antibiotics, Antineoplastic - administration & dosage Biomarkers, Tumor Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell Line, Tumor Cell Survival - drug effects DNA-Binding Proteins - metabolism Dose-Response Relationship, Drug Doxorubicin - administration & dosage Drug Resistance, Neoplasm Exonucleases Exoribonucleases Gene Expression Regulation, Neoplastic - drug effects Genes, Tumor Suppressor Humans Neoplasm Proteins Nuclear Proteins - metabolism Tumor Protein p73 Tumor Suppressor Protein p53 - metabolism Tumor Suppressor Proteins |
| title | p73-dependent induction of 14-3-3sigma increases the chemo-sensitivity of drug-resistant human breast cancers |
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