Real-time evaluation of p53 oscillatory behavior in vivo using bioluminescent imaging
p53 is a key mediator of cellular response to stress, and, although its function has been carefully evaluated in vitro, noninvasive evaluation of the transcriptional activity of p53 in live animals has not been reported. To this end, we developed a transgenic mouse model wherein the firefly lucifera...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2006-08, Vol.66 (15), p.7482-7489 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | HAMSTRA, Daniel A BHOJANI, Mahaveer S GRIFFIN, Laura B LAXMAN, Bharathi ROSS, Brian D REHEMTULLA, Alnawaz |
| description | p53 is a key mediator of cellular response to stress, and, although its function has been carefully evaluated in vitro, noninvasive evaluation of the transcriptional activity of p53 in live animals has not been reported. To this end, we developed a transgenic mouse model wherein the firefly luciferase gene expression was dependent on the p53-responsive P2 promoter from the murine double minute 2 (MDM2) gene. Bioluminescence activity following ionizing radiation was shown to be dose, time, and p53 dependent. In addition, expression of both p53 and its activated form as well as the expression of p53 target genes (MDM2 and p21) correlated with bioluminescence activity. Temporal evaluation of p53 activity following ionizing radiation showed a distinct oscillatory pattern, which confirmed the oscillations observed previously in cultured cells. In addition, the kinetics of oscillations were altered by pretreatment with radiation-modifying agents. These results show the use of this mouse model in enhancing our understanding of the transcriptional role of p53 in vivo. |
| doi_str_mv | 10.1158/0008-5472.can-06-1405 |
| format | Article |
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To this end, we developed a transgenic mouse model wherein the firefly luciferase gene expression was dependent on the p53-responsive P2 promoter from the murine double minute 2 (MDM2) gene. Bioluminescence activity following ionizing radiation was shown to be dose, time, and p53 dependent. In addition, expression of both p53 and its activated form as well as the expression of p53 target genes (MDM2 and p21) correlated with bioluminescence activity. Temporal evaluation of p53 activity following ionizing radiation showed a distinct oscillatory pattern, which confirmed the oscillations observed previously in cultured cells. In addition, the kinetics of oscillations were altered by pretreatment with radiation-modifying agents. These results show the use of this mouse model in enhancing our understanding of the transcriptional role of p53 in vivo.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.can-06-1405</identifier><identifier>PMID: 16885345</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Biological and medical sciences ; Biological Clocks ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; DNA Damage ; Feedback ; Fundamental and applied biological sciences. Psychology ; Genes, p53 ; Luciferases, Firefly - genetics ; Luminescent Measurements - methods ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Molecular and cellular biology ; Promoter Regions, Genetic ; Proto-Oncogene Proteins c-mdm2 - genetics ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Tumor Suppressor Protein p53 - physiology ; Up-Regulation</subject><ispartof>Cancer research (Chicago, Ill.), 2006-08, Vol.66 (15), p.7482-7489</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-cb3887ae294c5512cbf98cc054560181a3364231ac5261e34372479866416ee03</citedby><cites>FETCH-LOGICAL-c468t-cb3887ae294c5512cbf98cc054560181a3364231ac5261e34372479866416ee03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,3357,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18012652$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16885345$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HAMSTRA, Daniel A</creatorcontrib><creatorcontrib>BHOJANI, Mahaveer S</creatorcontrib><creatorcontrib>GRIFFIN, Laura B</creatorcontrib><creatorcontrib>LAXMAN, Bharathi</creatorcontrib><creatorcontrib>ROSS, Brian D</creatorcontrib><creatorcontrib>REHEMTULLA, Alnawaz</creatorcontrib><title>Real-time evaluation of p53 oscillatory behavior in vivo using bioluminescent imaging</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>p53 is a key mediator of cellular response to stress, and, although its function has been carefully evaluated in vitro, noninvasive evaluation of the transcriptional activity of p53 in live animals has not been reported. To this end, we developed a transgenic mouse model wherein the firefly luciferase gene expression was dependent on the p53-responsive P2 promoter from the murine double minute 2 (MDM2) gene. Bioluminescence activity following ionizing radiation was shown to be dose, time, and p53 dependent. In addition, expression of both p53 and its activated form as well as the expression of p53 target genes (MDM2 and p21) correlated with bioluminescence activity. Temporal evaluation of p53 activity following ionizing radiation showed a distinct oscillatory pattern, which confirmed the oscillations observed previously in cultured cells. In addition, the kinetics of oscillations were altered by pretreatment with radiation-modifying agents. These results show the use of this mouse model in enhancing our understanding of the transcriptional role of p53 in vivo.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biological Clocks</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>DNA Damage</subject><subject>Feedback</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes, p53</subject><subject>Luciferases, Firefly - genetics</subject><subject>Luminescent Measurements - methods</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Transgenic</subject><subject>Molecular and cellular biology</subject><subject>Promoter Regions, Genetic</subject><subject>Proto-Oncogene Proteins c-mdm2 - genetics</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumor Suppressor Protein p53 - physiology</subject><subject>Up-Regulation</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLAzEQgIMoWh8_QclFb1szSSabHkvxBUVB9ByyMauR3U3d7Bb6702x6NHDEGb4JjPzEXIObAqA-poxpguUJZ862xVMFSAZ7pEJoNBFKSXuk8kvc0SOU_rMKQLDQ3IESmsUEifk9dnbphhC66lf22a0Q4gdjTVdoaAxudA0doj9hlb-w65D7Gno6DqsIx1T6N5pFWIztqHzyfluoKG177l8Sg5q2yR_tntPyOvtzcvivlg-3T0s5svCSaWHwlVC69J6PpMOEbir6pl2jqFExUCDFUJJLsA65Aq8kKLkspxppSQo75k4IVc__676-DX6NJg25EXyzp2PYzJKl4Al5_-CMJMqh84g_oCujyn1vjarPh_VbwwwsxVvtlLNVqpZzB8NU2YrPvdd7AaMVevf_rp2pjNwuQNscrape9u5kP44zYAr5OIb8hOKjA</recordid><startdate>20060801</startdate><enddate>20060801</enddate><creator>HAMSTRA, Daniel A</creator><creator>BHOJANI, Mahaveer S</creator><creator>GRIFFIN, Laura B</creator><creator>LAXMAN, Bharathi</creator><creator>ROSS, Brian D</creator><creator>REHEMTULLA, Alnawaz</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20060801</creationdate><title>Real-time evaluation of p53 oscillatory behavior in vivo using bioluminescent imaging</title><author>HAMSTRA, Daniel A ; BHOJANI, Mahaveer S ; GRIFFIN, Laura B ; LAXMAN, Bharathi ; ROSS, Brian D ; REHEMTULLA, Alnawaz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-cb3887ae294c5512cbf98cc054560181a3364231ac5261e34372479866416ee03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biological Clocks</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>DNA Damage</topic><topic>Feedback</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genes, p53</topic><topic>Luciferases, Firefly - genetics</topic><topic>Luminescent Measurements - methods</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Transgenic</topic><topic>Molecular and cellular biology</topic><topic>Promoter Regions, Genetic</topic><topic>Proto-Oncogene Proteins c-mdm2 - genetics</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumor Suppressor Protein p53 - physiology</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HAMSTRA, Daniel A</creatorcontrib><creatorcontrib>BHOJANI, Mahaveer S</creatorcontrib><creatorcontrib>GRIFFIN, Laura B</creatorcontrib><creatorcontrib>LAXMAN, Bharathi</creatorcontrib><creatorcontrib>ROSS, Brian D</creatorcontrib><creatorcontrib>REHEMTULLA, Alnawaz</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>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HAMSTRA, Daniel A</au><au>BHOJANI, Mahaveer S</au><au>GRIFFIN, Laura B</au><au>LAXMAN, Bharathi</au><au>ROSS, Brian D</au><au>REHEMTULLA, Alnawaz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Real-time evaluation of p53 oscillatory behavior in vivo using bioluminescent imaging</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2006-08-01</date><risdate>2006</risdate><volume>66</volume><issue>15</issue><spage>7482</spage><epage>7489</epage><pages>7482-7489</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>p53 is a key mediator of cellular response to stress, and, although its function has been carefully evaluated in vitro, noninvasive evaluation of the transcriptional activity of p53 in live animals has not been reported. To this end, we developed a transgenic mouse model wherein the firefly luciferase gene expression was dependent on the p53-responsive P2 promoter from the murine double minute 2 (MDM2) gene. Bioluminescence activity following ionizing radiation was shown to be dose, time, and p53 dependent. In addition, expression of both p53 and its activated form as well as the expression of p53 target genes (MDM2 and p21) correlated with bioluminescence activity. Temporal evaluation of p53 activity following ionizing radiation showed a distinct oscillatory pattern, which confirmed the oscillations observed previously in cultured cells. In addition, the kinetics of oscillations were altered by pretreatment with radiation-modifying agents. These results show the use of this mouse model in enhancing our understanding of the transcriptional role of p53 in vivo.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>16885345</pmid><doi>10.1158/0008-5472.can-06-1405</doi><tpages>8</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Biological Clocks Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes DNA Damage Feedback Fundamental and applied biological sciences. Psychology Genes, p53 Luciferases, Firefly - genetics Luminescent Measurements - methods Mice Mice, Inbred BALB C Mice, Transgenic Molecular and cellular biology Promoter Regions, Genetic Proto-Oncogene Proteins c-mdm2 - genetics Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Tumor Suppressor Protein p53 - physiology Up-Regulation |
| title | Real-time evaluation of p53 oscillatory behavior in vivo using bioluminescent imaging |
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