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EGF-mediated induction of Mcl-1 at the switch to lactation is essential for alveolar cell survival

Fu, Nai Yang; Rios, Anne C.; Pal, Bhupinder; Soetanto, Rina; Lun, Aaron T. L.; Liu, Kevin; Beck, Tamara; Best, Sarah A.; Vaillant, François; Bouillet, Philippe; Strasser, Andreas; Preiss, Thomas; Smyth, Gordon K.; Lindeman, Geoffrey J.; Visvader, Jane E.

Description

Expansion and remodelling of the mammary epithelium requires a tight balance between cellular proliferation, differentiation and death. To explore cell survival versus cell death decisions in this organ, we deleted the pro-survival gene Mcl-1 in the mammary epithelium. Mcl-1 was found to be essential at multiple developmental stages including morphogenesis in puberty and alveologenesis in pregnancy. Moreover, Mcl-1-deficient basal cells were virtually devoid of repopulating activity, suggesting...[Show more]

dc.contributor.authorFu, Nai Yang
dc.contributor.authorRios, Anne C.
dc.contributor.authorPal, Bhupinder
dc.contributor.authorSoetanto, Rina
dc.contributor.authorLun, Aaron T. L.
dc.contributor.authorLiu, Kevin
dc.contributor.authorBeck, Tamara
dc.contributor.authorBest, Sarah A.
dc.contributor.authorVaillant, François
dc.contributor.authorBouillet, Philippe
dc.contributor.authorStrasser, Andreas
dc.contributor.authorPreiss, Thomas
dc.contributor.authorSmyth, Gordon K.
dc.contributor.authorLindeman, Geoffrey J.
dc.contributor.authorVisvader, Jane E.
dc.date.accessioned2015-06-23T04:50:40Z
dc.date.available2015-06-23T04:50:40Z
dc.identifier.issn1465-7392
dc.identifier.urihttp://hdl.handle.net/1885/14103
dc.description.abstractExpansion and remodelling of the mammary epithelium requires a tight balance between cellular proliferation, differentiation and death. To explore cell survival versus cell death decisions in this organ, we deleted the pro-survival gene Mcl-1 in the mammary epithelium. Mcl-1 was found to be essential at multiple developmental stages including morphogenesis in puberty and alveologenesis in pregnancy. Moreover, Mcl-1-deficient basal cells were virtually devoid of repopulating activity, suggesting that this gene is required for stem cell function. Profound upregulation of the Mcl-1 protein was evident in alveolar cells at the switch to lactation, and Mcl-1 deficiency impaired lactation. Interestingly, EGF was identified as one of the most highly upregulated genes on lactogenesis and inhibition of EGF or mTOR signalling markedly impaired lactation, with concomitant decreases in Mcl-1 and phosphorylated ribosomal protein S6. These data demonstrate that Mcl-1 is essential for mammopoiesis and identify EGF as a critical trigger of Mcl-1 translation to ensure survival of milk-producing alveolar cells.
dc.publisherNature Publishing Group
dc.rights© 2015 Macmillan Publishers Limited
dc.sourceNature Cell Biology
dc.subjectanimals
dc.subjectapoptosis
dc.subjectbase sequence
dc.subjectcell differentiation
dc.subjectcell line
dc.subjectcell proliferation
dc.subjectcell survival
dc.subjectepidermal growth factor
dc.subjectfemale
dc.subjectgene knockout techniques
dc.subjectlactation
dc.subjectmammary glands, animal
dc.subjectmice
dc.subjectmice, inbred c57bl
dc.subjectmyeloid cell leukemia sequence 1 protein
dc.subjectphosphorylation
dc.subjectpregnancy
dc.subjectribosomal protein s6
dc.subjectsequence analysis, rna
dc.subjectstem cells
dc.subjecttor serine-threonine kinases
dc.subjectup-regulation
dc.titleEGF-mediated induction of Mcl-1 at the switch to lactation is essential for alveolar cell survival
dc.typeJournal article
local.identifier.citationvolume17
dcterms.dateAccepted2015-01-19
dc.date.issued2015-03-02
local.identifier.absfor060100 - BIOCHEMISTRY AND CELL BIOLOGY
local.identifier.absfor060400 - GENETICS
local.identifier.ariespublicationa383154xPUB1333
local.publisher.urlhttp://www.nature.com/
local.type.statusPublished Version
local.contributor.affiliationSoetanto, R., Genome Biology Department, John Curtin School of Medical Research, The Australian National University
local.contributor.affiliationPreiss, T., Genome Biology Department, John Curtin School of Medical Research, The Australian National University
local.identifier.essn1476-4679
local.bibliographicCitation.issue4
local.bibliographicCitation.startpage365
local.bibliographicCitation.lastpage375
local.identifier.doi10.1038/ncb3117
dc.date.updated2015-12-10T10:35:30Z
local.identifier.scopusID2-s2.0-84925969713
CollectionsANU Research Publications

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