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

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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

61 Citaten (Scopus)

Samenvatting

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 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.

Originele taal-2Engels
Pagina's (van-tot)365-375
Aantal pagina's11
TijdschriftNature Cell Biology
Volume17
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - 30 apr. 2015
Extern gepubliceerdJa

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