Journal article
EGF-mediated induction of Mcl-1 at the switch to lactation is essential for alveolar cell survival
NY Fu, AC Rios, B Pal, R Soetanto, ATL Lun, K Liu, T Beck, SA Best, F Vaillant, P Bouillet, A Strasser, T Preiss, GK Smyth, GJ Lindeman, JE Visvader
Nature Cell Biology | NATURE PUBLISHING GROUP | Published : 2015
DOI: 10.1038/ncb3117
Abstract
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. Interes..
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Awarded by National Breast Cancer Foundation
Funding Acknowledgements
We are grateful to J. Takeda and M. Takaishi for the gift of K5-cre transgenic mice and S. Glaser for provision of an We thank D. Huang for advice. We also thank J. L. Clancy, S. K. Archer and G. III./irtan for assistance with the polysome experiments, Py Helbert for genotyping, and the Ai iii FACS, Imaging and HistirTogy Hcilities il TI HI This work was supported by the Australian National Illealth and Medical Research Council (INHIMRC) grants no. 1016701, no. 1024852, no. 1086727; NHMRC RI S the VDtorian State Government through RICA Minding of the Victorian Breast Cancer Reseamh Consortium and Operational infrastructure Support; and the Australian Cancer Research Foundation. N.Y.F. and. are supported by a National Breast Cancer Foundation (NB( F)/Cure Cancer Australia FellowshM; AT.L.L. by an Elizabeth and Vernon Puzey Scholarship from the University of Metbaurne; S. IF. by a N IV R 1 ystgraduate ScholarshM to 1017256; P.B., G.K.S. and G.I.L by NITAIRC Fell ships no. 1042629, no. 1058892, no. 637307; and J.E. V. by an Australia Fellowship.