Identification of both Myt-1 and Wee-1 as necessary mediators of the p21-independent inactivation of the cdc-2/cyclin B1 complex and growth inhibition of TRAMP cancer cells by genistein
BACKGROUND The G2/M cell‐cycle arrest is one mechanism by which genistein exerts its anti‐proliferative effects, and the proposed underlying causes encompass the transcriptional repression of cyclin B1 and the activation of p21. However, the involvement of upstream kinases Myt‐1 and Wee‐1 in this ar...
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| Veröffentlicht in: | The Prostate 2006-10, Vol.66 (14), p.1542-1555 |
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| container_title | The Prostate |
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| creator | Touny, Lara H. El Banerjee, Partha P. |
| description | BACKGROUND
The G2/M cell‐cycle arrest is one mechanism by which genistein exerts its anti‐proliferative effects, and the proposed underlying causes encompass the transcriptional repression of cyclin B1 and the activation of p21. However, the involvement of upstream kinases Myt‐1 and Wee‐1 in this arrest remains to be elucidated.
METHODS
Myt‐1 and Wee‐1 modulation by genistein was examined via Western blot analysis and the effect of their inhibition by siRNA on cyclin B1 levels/localization, cdc2 kinase activity, and cellular proliferation of genistein‐treated TRAMP‐C2 cells was determined.
RESULTS
The sustained G2/M arrest by genistein in TRAMP‐C2 cells is associated with increased phospho‐cdc2(Tyr15), decreased cdc2 protein, and cytoplasmic retention of cyclinB1, resulting in decreased cdc2 kinase activity independently of p21. Genistein treatment increased Myt‐1 levels and decreased Wee‐1 phosphorylation. Downregulation of Myt‐1 and Wee‐1 by siRNA restored cdc2 levels, its kinase activity, cyclinB1 nuclear localization, and partially restored cell proliferation of genistein‐treated cells.
CONCLUSIONS
Myt‐1 and Wee‐1 rather than p21 are necessary for genistein‐induced G2/M arrest in TRAMP‐C2 cells and their inhibition partially restores proliferation of TRAMP‐C2 cells in the presence of genistein. Prostate 66: 1542–1555, 2006. © 2006 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/pros.20495 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_68825281</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>68825281</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3965-31a55ee440b377b8d868dc1f835022a7fd061ec39954392d22d29eee7760fb273</originalsourceid><addsrcrecordid>eNpFkd1O3DAQhS3Uqmxpb3iAyle9C_gntpNLisoWabcgoOXScpwJ6zbrpLEXyKPxdji7QCVLHsnfmRmfg9AhJUeUEHbcD104YiQvxR6aUVKqjJBcvEMzwhTJcsrVPvoYwh9CEk7YB7RPZclyKcUMPZ3X4KNrnDXRdR53Da66uMLLMWYUG1_jW4CpCtiDhRDMMOI11M7EbggTHleAe0Yz52vowU_tsPPGRnf_1nJibG0zdmxH2zqPv1Fsu3XfwuN2xt3QPaShzq9c5V5FN1cny0tsjbcwYAttG3A14jvwLkRw_hN635g2wOeX-wD9Ovt-c_ojW1zMz09PFpnlpRQZp0YIgDwnFVeqKupCFrWlTcEFYcyopiaSQmJLkfOS1SydEgCUkqSpmOIH6Ouub7L53wZC1GsXpnWMh24TtCwKJlhBE_jlBdxUySHdD26d3NKvZieA7oAH18L4_53oKUY9xai3MerLq4vrbZU02U4zffrxTWOGv1oqroS-_TnXi6USv6_npeb8GeS0oCE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>68825281</pqid></control><display><type>article</type><title>Identification of both Myt-1 and Wee-1 as necessary mediators of the p21-independent inactivation of the cdc-2/cyclin B1 complex and growth inhibition of TRAMP cancer cells by genistein</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Touny, Lara H. El ; Banerjee, Partha P.</creator><creatorcontrib>Touny, Lara H. El ; Banerjee, Partha P.</creatorcontrib><description>BACKGROUND
The G2/M cell‐cycle arrest is one mechanism by which genistein exerts its anti‐proliferative effects, and the proposed underlying causes encompass the transcriptional repression of cyclin B1 and the activation of p21. However, the involvement of upstream kinases Myt‐1 and Wee‐1 in this arrest remains to be elucidated.
METHODS
Myt‐1 and Wee‐1 modulation by genistein was examined via Western blot analysis and the effect of their inhibition by siRNA on cyclin B1 levels/localization, cdc2 kinase activity, and cellular proliferation of genistein‐treated TRAMP‐C2 cells was determined.
RESULTS
The sustained G2/M arrest by genistein in TRAMP‐C2 cells is associated with increased phospho‐cdc2(Tyr15), decreased cdc2 protein, and cytoplasmic retention of cyclinB1, resulting in decreased cdc2 kinase activity independently of p21. Genistein treatment increased Myt‐1 levels and decreased Wee‐1 phosphorylation. Downregulation of Myt‐1 and Wee‐1 by siRNA restored cdc2 levels, its kinase activity, cyclinB1 nuclear localization, and partially restored cell proliferation of genistein‐treated cells.
CONCLUSIONS
Myt‐1 and Wee‐1 rather than p21 are necessary for genistein‐induced G2/M arrest in TRAMP‐C2 cells and their inhibition partially restores proliferation of TRAMP‐C2 cells in the presence of genistein. Prostate 66: 1542–1555, 2006. © 2006 Wiley‐Liss, Inc.</description><identifier>ISSN: 0270-4137</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.20495</identifier><identifier>PMID: 16924665</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adenocarcinoma - drug therapy ; Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Animals ; Anticarcinogenic Agents - pharmacology ; Apoptosis - drug effects ; Aurora Kinases ; cdc2 kinase ; CDC2 Protein Kinase - antagonists & inhibitors ; CDC2 Protein Kinase - metabolism ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Cell Division - drug effects ; Cell Nucleus - metabolism ; Cyclin B - metabolism ; Cyclin B1 ; Cyclin-Dependent Kinase Inhibitor p21 - metabolism ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Dose-Response Relationship, Drug ; G2 Phase - drug effects ; genistein ; Genistein - pharmacology ; Male ; Mice ; Mice, Transgenic ; Myt-1 ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Prostatic Neoplasms - drug therapy ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Protein-Serine-Threonine Kinases - metabolism ; Protein-Tyrosine Kinases - genetics ; Protein-Tyrosine Kinases - metabolism ; RNA, Small Interfering ; TRAMP ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Wee-1</subject><ispartof>The Prostate, 2006-10, Vol.66 (14), p.1542-1555</ispartof><rights>Copyright © 2006 Wiley‐Liss, Inc.</rights><rights>(c) 2006 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3965-31a55ee440b377b8d868dc1f835022a7fd061ec39954392d22d29eee7760fb273</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpros.20495$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpros.20495$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27926,27927,45576,45577</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16924665$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Touny, Lara H. El</creatorcontrib><creatorcontrib>Banerjee, Partha P.</creatorcontrib><title>Identification of both Myt-1 and Wee-1 as necessary mediators of the p21-independent inactivation of the cdc-2/cyclin B1 complex and growth inhibition of TRAMP cancer cells by genistein</title><title>The Prostate</title><addtitle>Prostate</addtitle><description>BACKGROUND
The G2/M cell‐cycle arrest is one mechanism by which genistein exerts its anti‐proliferative effects, and the proposed underlying causes encompass the transcriptional repression of cyclin B1 and the activation of p21. However, the involvement of upstream kinases Myt‐1 and Wee‐1 in this arrest remains to be elucidated.
METHODS
Myt‐1 and Wee‐1 modulation by genistein was examined via Western blot analysis and the effect of their inhibition by siRNA on cyclin B1 levels/localization, cdc2 kinase activity, and cellular proliferation of genistein‐treated TRAMP‐C2 cells was determined.
RESULTS
The sustained G2/M arrest by genistein in TRAMP‐C2 cells is associated with increased phospho‐cdc2(Tyr15), decreased cdc2 protein, and cytoplasmic retention of cyclinB1, resulting in decreased cdc2 kinase activity independently of p21. Genistein treatment increased Myt‐1 levels and decreased Wee‐1 phosphorylation. Downregulation of Myt‐1 and Wee‐1 by siRNA restored cdc2 levels, its kinase activity, cyclinB1 nuclear localization, and partially restored cell proliferation of genistein‐treated cells.
CONCLUSIONS
Myt‐1 and Wee‐1 rather than p21 are necessary for genistein‐induced G2/M arrest in TRAMP‐C2 cells and their inhibition partially restores proliferation of TRAMP‐C2 cells in the presence of genistein. Prostate 66: 1542–1555, 2006. © 2006 Wiley‐Liss, Inc.</description><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Animals</subject><subject>Anticarcinogenic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Aurora Kinases</subject><subject>cdc2 kinase</subject><subject>CDC2 Protein Kinase - antagonists & inhibitors</subject><subject>CDC2 Protein Kinase - metabolism</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Division - drug effects</subject><subject>Cell Nucleus - metabolism</subject><subject>Cyclin B - metabolism</subject><subject>Cyclin B1</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>G2 Phase - drug effects</subject><subject>genistein</subject><subject>Genistein - pharmacology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Myt-1</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Protein-Tyrosine Kinases - genetics</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>RNA, Small Interfering</subject><subject>TRAMP</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Wee-1</subject><issn>0270-4137</issn><issn>1097-0045</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkd1O3DAQhS3Uqmxpb3iAyle9C_gntpNLisoWabcgoOXScpwJ6zbrpLEXyKPxdji7QCVLHsnfmRmfg9AhJUeUEHbcD104YiQvxR6aUVKqjJBcvEMzwhTJcsrVPvoYwh9CEk7YB7RPZclyKcUMPZ3X4KNrnDXRdR53Da66uMLLMWYUG1_jW4CpCtiDhRDMMOI11M7EbggTHleAe0Yz52vowU_tsPPGRnf_1nJibG0zdmxH2zqPv1Fsu3XfwuN2xt3QPaShzq9c5V5FN1cny0tsjbcwYAttG3A14jvwLkRw_hN635g2wOeX-wD9Ovt-c_ojW1zMz09PFpnlpRQZp0YIgDwnFVeqKupCFrWlTcEFYcyopiaSQmJLkfOS1SydEgCUkqSpmOIH6Ouub7L53wZC1GsXpnWMh24TtCwKJlhBE_jlBdxUySHdD26d3NKvZieA7oAH18L4_53oKUY9xai3MerLq4vrbZU02U4zffrxTWOGv1oqroS-_TnXi6USv6_npeb8GeS0oCE</recordid><startdate>20061001</startdate><enddate>20061001</enddate><creator>Touny, Lara H. El</creator><creator>Banerjee, Partha P.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20061001</creationdate><title>Identification of both Myt-1 and Wee-1 as necessary mediators of the p21-independent inactivation of the cdc-2/cyclin B1 complex and growth inhibition of TRAMP cancer cells by genistein</title><author>Touny, Lara H. El ; Banerjee, Partha P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3965-31a55ee440b377b8d868dc1f835022a7fd061ec39954392d22d29eee7760fb273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - metabolism</topic><topic>Adenocarcinoma - pathology</topic><topic>Animals</topic><topic>Anticarcinogenic Agents - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Aurora Kinases</topic><topic>cdc2 kinase</topic><topic>CDC2 Protein Kinase - antagonists & inhibitors</topic><topic>CDC2 Protein Kinase - metabolism</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Division - drug effects</topic><topic>Cell Nucleus - metabolism</topic><topic>Cyclin B - metabolism</topic><topic>Cyclin B1</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>G2 Phase - drug effects</topic><topic>genistein</topic><topic>Genistein - pharmacology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Myt-1</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Protein-Tyrosine Kinases - genetics</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>RNA, Small Interfering</topic><topic>TRAMP</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Wee-1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Touny, Lara H. El</creatorcontrib><creatorcontrib>Banerjee, Partha P.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Touny, Lara H. El</au><au>Banerjee, Partha P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of both Myt-1 and Wee-1 as necessary mediators of the p21-independent inactivation of the cdc-2/cyclin B1 complex and growth inhibition of TRAMP cancer cells by genistein</atitle><jtitle>The Prostate</jtitle><addtitle>Prostate</addtitle><date>2006-10-01</date><risdate>2006</risdate><volume>66</volume><issue>14</issue><spage>1542</spage><epage>1555</epage><pages>1542-1555</pages><issn>0270-4137</issn><eissn>1097-0045</eissn><abstract>BACKGROUND
The G2/M cell‐cycle arrest is one mechanism by which genistein exerts its anti‐proliferative effects, and the proposed underlying causes encompass the transcriptional repression of cyclin B1 and the activation of p21. However, the involvement of upstream kinases Myt‐1 and Wee‐1 in this arrest remains to be elucidated.
METHODS
Myt‐1 and Wee‐1 modulation by genistein was examined via Western blot analysis and the effect of their inhibition by siRNA on cyclin B1 levels/localization, cdc2 kinase activity, and cellular proliferation of genistein‐treated TRAMP‐C2 cells was determined.
RESULTS
The sustained G2/M arrest by genistein in TRAMP‐C2 cells is associated with increased phospho‐cdc2(Tyr15), decreased cdc2 protein, and cytoplasmic retention of cyclinB1, resulting in decreased cdc2 kinase activity independently of p21. Genistein treatment increased Myt‐1 levels and decreased Wee‐1 phosphorylation. Downregulation of Myt‐1 and Wee‐1 by siRNA restored cdc2 levels, its kinase activity, cyclinB1 nuclear localization, and partially restored cell proliferation of genistein‐treated cells.
CONCLUSIONS
Myt‐1 and Wee‐1 rather than p21 are necessary for genistein‐induced G2/M arrest in TRAMP‐C2 cells and their inhibition partially restores proliferation of TRAMP‐C2 cells in the presence of genistein. Prostate 66: 1542–1555, 2006. © 2006 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>16924665</pmid><doi>10.1002/pros.20495</doi><tpages>14</tpages></addata></record> |
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| subjects | Adenocarcinoma - drug therapy Adenocarcinoma - metabolism Adenocarcinoma - pathology Animals Anticarcinogenic Agents - pharmacology Apoptosis - drug effects Aurora Kinases cdc2 kinase CDC2 Protein Kinase - antagonists & inhibitors CDC2 Protein Kinase - metabolism Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Division - drug effects Cell Nucleus - metabolism Cyclin B - metabolism Cyclin B1 Cyclin-Dependent Kinase Inhibitor p21 - metabolism DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Dose-Response Relationship, Drug G2 Phase - drug effects genistein Genistein - pharmacology Male Mice Mice, Transgenic Myt-1 Nuclear Proteins - genetics Nuclear Proteins - metabolism Prostatic Neoplasms - drug therapy Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Protein-Serine-Threonine Kinases - metabolism Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism RNA, Small Interfering TRAMP Transcription Factors - genetics Transcription Factors - metabolism Wee-1 |
| title | Identification of both Myt-1 and Wee-1 as necessary mediators of the p21-independent inactivation of the cdc-2/cyclin B1 complex and growth inhibition of TRAMP cancer cells by genistein |
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