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dc.contributor.authorXia, Fang
dc.contributor.authorAltieri, Dario C.
dc.date2022-08-11T08:09:50.000
dc.date.accessioned2022-08-23T16:45:19Z
dc.date.available2022-08-23T16:45:19Z
dc.date.issued2006-04-06
dc.date.submitted2008-06-18
dc.identifier.citationCancer Res. 2006 Apr 1;66(7):3392-5. <a href="http://dx.doi.org/10.1158/0008-5472.CAN-05-4537">Link to article on publisher's site</a>
dc.identifier.issn0008-5472 (Print)
dc.identifier.doi10.1158/0008-5472.CAN-05-4537
dc.identifier.pmid16585159
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40657
dc.description.abstractSurvivin is an essential mitotic gene, and this has been speculated to reflect its primary function in development and cancer. Here, we generated a knock-in transgenic mouse (SVVp-GFP) in which a green fluorescent protein (GFP) reporter gene was placed under the control of the survivin promoter that regulates transcription at mitosis. The expression of endogenous survivin was widespread in mouse tissues during development and shortly after birth. In contrast, GFP reactivity was undetectable in transgenic mouse embryos, and was largely limited postnatally to mitotic cells in the testes. Double transgenic mice generated in the tumor-prone Min/+ background exhibited intestinal adenomas that strongly expressed endogenous survivin, but only isolated GFP-positive cells. Conversely, dysplastic adenomas (16%) stained intensely for GFP, and revealed focal reactivity for mutant, but not wild-type, p53. The expression of GFP was increased by approximately 10-fold in p53(-/-) as opposed to p53(+/+) HCT116 colorectal cancer cells, and reintroduction of p53 in p53(-/-) cells abolished GFP expression. Therefore, the mitotic transcription of the survivin gene is highly restricted in vivo, and unexpectedly negatively regulated by p53. Contrary to a commonly held view, the dominant function(s) of survivin in development and tumor ontogeny are largely cell cycle-independent.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16585159&dopt=Abstract">Link to article in PubMed</a>
dc.subjectAnimals
dc.subjectBase Sequence
dc.subjectCell Cycle
dc.subjectCell Transformation, Neoplastic
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectGreen Fluorescent Proteins
dc.subjectHCT116 Cells
dc.subjectHela Cells
dc.subjectHumans
dc.subjectMice
dc.subjectMice, Transgenic
dc.subjectMicrotubule-Associated Proteins
dc.subjectMitosis
dc.subjectMolecular Sequence Data
dc.subjectPromoter Regions (Genetics)
dc.subjectTumor Suppressor Protein p53
dc.subjectCancer Biology
dc.subjectGenetics and Genomics
dc.titleMitosis-independent survivin gene expression in vivo and regulation by p53
dc.typeJournal Article
dc.source.journaltitleCancer research
dc.source.volume66
dc.source.issue7
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1345&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/346
dc.identifier.contextkey533054
refterms.dateFOA2022-08-23T16:45:19Z
html.description.abstract<p>Survivin is an essential mitotic gene, and this has been speculated to reflect its primary function in development and cancer. Here, we generated a knock-in transgenic mouse (SVVp-GFP) in which a green fluorescent protein (GFP) reporter gene was placed under the control of the survivin promoter that regulates transcription at mitosis. The expression of endogenous survivin was widespread in mouse tissues during development and shortly after birth. In contrast, GFP reactivity was undetectable in transgenic mouse embryos, and was largely limited postnatally to mitotic cells in the testes. Double transgenic mice generated in the tumor-prone Min/+ background exhibited intestinal adenomas that strongly expressed endogenous survivin, but only isolated GFP-positive cells. Conversely, dysplastic adenomas (16%) stained intensely for GFP, and revealed focal reactivity for mutant, but not wild-type, p53. The expression of GFP was increased by approximately 10-fold in p53(-/-) as opposed to p53(+/+) HCT116 colorectal cancer cells, and reintroduction of p53 in p53(-/-) cells abolished GFP expression. Therefore, the mitotic transcription of the survivin gene is highly restricted in vivo, and unexpectedly negatively regulated by p53. Contrary to a commonly held view, the dominant function(s) of survivin in development and tumor ontogeny are largely cell cycle-independent.</p>
dc.identifier.submissionpathoapubs/346
dc.contributor.departmentDepartment of Cancer Biology and the Cancer Center
dc.source.pages3392-5


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