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Article: The acetyltransferase Tip60 contributes to mammary tumorigenesis by modulating DNA repair

TitleThe acetyltransferase Tip60 contributes to mammary tumorigenesis by modulating DNA repair
Authors
Issue Date2016
Citation
Cell Death and Differentiation, 2016, v. 23, n. 7, p. 1198-1208 How to Cite?
AbstractThe acetyltransferase Tip60/Kat5 acetylates both histone and non-histone proteins, and is involved in a variety of biological processes. By acetylating p53, Tip60 controls p53-dependent transcriptional activity and so is implicated as a tumor suppressor. However, many breast cancers with low Tip60 also show p53 mutation, implying that Tip60 has a tumor suppressor function independent of its acetylation of p53. Here, we show in a p53-null mouse model of sporadic invasive breast adenocarcinoma that heterozygosity for Tip60 deletion promotes mammary tumorigenesis. Low Tip60 reduces DNA repair in normal and tumor mammary epithelial cells, both under resting conditions and following genotoxic stress. We demonstrate that Tip60 controls homologous recombination (HR)-directed DNA repair, and that Tip60 levels correlate inversely with a gene expression signature associated with defective HR-directed DNA repair. In human breast cancer data sets, Tip60 mRNA is downregulated, with low Tip60 levels correlating with p53 mutations in basal-like breast cancers. Our findings indicate that Tip60 is a novel breast tumor suppressor gene whose loss results in genomic instability leading to cancer formation.
Persistent Identifierhttp://hdl.handle.net/10722/292935
ISSN
2023 Impact Factor: 13.7
2023 SCImago Journal Rankings: 4.102
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBassi, C.-
dc.contributor.authorLi, Y. T.-
dc.contributor.authorKhu, K.-
dc.contributor.authorMateo, F.-
dc.contributor.authorBaniasadi, P. S.-
dc.contributor.authorElia, A.-
dc.contributor.authorMason, J.-
dc.contributor.authorStambolic, V.-
dc.contributor.authorPujana, M. A.-
dc.contributor.authorMak, T. W.-
dc.contributor.authorGorrini, C.-
dc.date.accessioned2020-11-17T14:57:32Z-
dc.date.available2020-11-17T14:57:32Z-
dc.date.issued2016-
dc.identifier.citationCell Death and Differentiation, 2016, v. 23, n. 7, p. 1198-1208-
dc.identifier.issn1350-9047-
dc.identifier.urihttp://hdl.handle.net/10722/292935-
dc.description.abstractThe acetyltransferase Tip60/Kat5 acetylates both histone and non-histone proteins, and is involved in a variety of biological processes. By acetylating p53, Tip60 controls p53-dependent transcriptional activity and so is implicated as a tumor suppressor. However, many breast cancers with low Tip60 also show p53 mutation, implying that Tip60 has a tumor suppressor function independent of its acetylation of p53. Here, we show in a p53-null mouse model of sporadic invasive breast adenocarcinoma that heterozygosity for Tip60 deletion promotes mammary tumorigenesis. Low Tip60 reduces DNA repair in normal and tumor mammary epithelial cells, both under resting conditions and following genotoxic stress. We demonstrate that Tip60 controls homologous recombination (HR)-directed DNA repair, and that Tip60 levels correlate inversely with a gene expression signature associated with defective HR-directed DNA repair. In human breast cancer data sets, Tip60 mRNA is downregulated, with low Tip60 levels correlating with p53 mutations in basal-like breast cancers. Our findings indicate that Tip60 is a novel breast tumor suppressor gene whose loss results in genomic instability leading to cancer formation.-
dc.languageeng-
dc.relation.ispartofCell Death and Differentiation-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleThe acetyltransferase Tip60 contributes to mammary tumorigenesis by modulating DNA repair-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/cdd.2015.173-
dc.identifier.pmid26915295-
dc.identifier.pmcidPMC4946888-
dc.identifier.scopuseid_2-s2.0-84959241163-
dc.identifier.volume23-
dc.identifier.issue7-
dc.identifier.spage1198-
dc.identifier.epage1208-
dc.identifier.eissn1476-5403-
dc.identifier.isiWOS:000377929500011-
dc.identifier.issnl1350-9047-

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