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Article: Subtle variations in Pten dose determine cancer susceptibility

TitleSubtle variations in Pten dose determine cancer susceptibility
Authors
Alimonti, ACarracedo, AClohessy, JGTrotman, LCNardella, CEgia, ASalmena, LSampieri, KHaveman, WJBrogi, ERichardson, ALZhang, JPandolfi, PP
Issue Date2010
PublisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
Citation
Nature Genetics, 2010, v. 42 n. 5, p. 454-458 How to Cite?
DOI: http://dx.doi.org/10.1038/ng.556
AbstractCancer susceptibility has been attributed to at least one heterozygous genetic alteration in a tumor suppressor gene (TSG). It has been hypothesized that subtle variations in TSG expression can promote cancer development. However, this hypothesis has not yet been definitively supported in vivo. Pten is a TSG frequently lost in human cancer and mutated in inherited cancer-predisposition syndromes. Here we analyze Pten hypermorphic mice (Pten hy/+), expressing 80% normal levels of Pten. Pten hy/+ mice develop a spectrum of tumors, with breast tumors occurring at the highest penetrance. All breast tumors analyzed here retained two intact copies of Pten and maintained Pten levels above heterozygosity. Notably, subtle downregulation of Pten altered the steady-state biology of the mammary tissues and the expression profiles of genes involved in cancer cell proliferation. We present an alterative working model for cancer development in which subtle reductions in the dose of TSGs predispose to tumorigenesis in a tissue-specific manner. © 2010 Nature America, Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/180738
ISSN
1061-4036
2023 Impact Factor: 31.7
2023 SCImago Journal Rankings: 17.300
ISI Accession Number ID
WOS:000277179500019
References
References in Scopus

 

DC FieldValueLanguage
dc.contributor.authorAlimonti, Aen_US
dc.contributor.authorCarracedo, Aen_US
dc.contributor.authorClohessy, JGen_US
dc.contributor.authorTrotman, LCen_US
dc.contributor.authorNardella, Cen_US
dc.contributor.authorEgia, Aen_US
dc.contributor.authorSalmena, Len_US
dc.contributor.authorSampieri, Ken_US
dc.contributor.authorHaveman, WJen_US
dc.contributor.authorBrogi, Een_US
dc.contributor.authorRichardson, ALen_US
dc.contributor.authorZhang, Jen_US
dc.contributor.authorPandolfi, PPen_US
dc.date.accessioned2013-01-28T01:42:08Z-
dc.date.available2013-01-28T01:42:08Z-
dc.date.issued2010en_US
dc.identifier.citationNature Genetics, 2010, v. 42 n. 5, p. 454-458en_US
dc.identifier.issn1061-4036en_US
dc.identifier.urihttp://hdl.handle.net/10722/180738-
dc.description.abstractCancer susceptibility has been attributed to at least one heterozygous genetic alteration in a tumor suppressor gene (TSG). It has been hypothesized that subtle variations in TSG expression can promote cancer development. However, this hypothesis has not yet been definitively supported in vivo. Pten is a TSG frequently lost in human cancer and mutated in inherited cancer-predisposition syndromes. Here we analyze Pten hypermorphic mice (Pten hy/+), expressing 80% normal levels of Pten. Pten hy/+ mice develop a spectrum of tumors, with breast tumors occurring at the highest penetrance. All breast tumors analyzed here retained two intact copies of Pten and maintained Pten levels above heterozygosity. Notably, subtle downregulation of Pten altered the steady-state biology of the mammary tissues and the expression profiles of genes involved in cancer cell proliferation. We present an alterative working model for cancer development in which subtle reductions in the dose of TSGs predispose to tumorigenesis in a tissue-specific manner. © 2010 Nature America, Inc. All rights reserved.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.comen_US
dc.relation.ispartofNature Geneticsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBreast Neoplasms - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Dosageen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshGenes, Tumor Suppressoren_US
dc.subject.meshGenetic Predisposition To Disease - Geneticsen_US
dc.subject.meshHeterozygoteen_US
dc.subject.meshHomozygoteen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMammary Neoplasms, Animal - Geneticsen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Transgenicen_US
dc.subject.meshModels, Geneticen_US
dc.subject.meshMutationen_US
dc.subject.meshPten Phosphohydrolase - Geneticsen_US
dc.titleSubtle variations in Pten dose determine cancer susceptibilityen_US
dc.typeArticleen_US
dc.identifier.emailZhang, J: jzhang1@hku.hken_US
dc.identifier.authorityZhang, J=rp01713en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/ng.556en_US
dc.identifier.pmid20400965-
dc.identifier.scopuseid_2-s2.0-77951765345en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77951765345&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume42en_US
dc.identifier.issue5en_US
dc.identifier.spage454en_US
dc.identifier.epage458en_US
dc.identifier.isiWOS:000277179500019-
dc.publisher.placeUnited Statesen_US
dc.identifier.f10003099964-
dc.identifier.scopusauthoridAlimonti, A=7003443619en_US
dc.identifier.scopusauthoridCarracedo, A=8549430700en_US
dc.identifier.scopusauthoridClohessy, JG=14318994000en_US
dc.identifier.scopusauthoridTrotman, LC=6603486818en_US
dc.identifier.scopusauthoridNardella, C=24721817100en_US
dc.identifier.scopusauthoridEgia, A=12647355200en_US
dc.identifier.scopusauthoridSalmena, L=6507806834en_US
dc.identifier.scopusauthoridSampieri, K=12791887700en_US
dc.identifier.scopusauthoridHaveman, WJ=36106039000en_US
dc.identifier.scopusauthoridBrogi, E=6701428901en_US
dc.identifier.scopusauthoridRichardson, AL=7402533820en_US
dc.identifier.scopusauthoridZhang, J=22137260600en_US
dc.identifier.scopusauthoridPandolfi, PP=7005021176en_US
dc.identifier.issnl1061-4036-

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