%0 Journal Article
%~ PubMed
%A Moran-Jones, Kim
%A Ledger, Anita
%A Naylor, Matthew J
%T β1 integrin deletion enhances progression of prostate cancer in the TRAMP mouse model.
%B Scientific Reports
%D 2012
%C United Kingdom
%I Nature Publishing Group
%V 2
%N 
%P 526
%@ 2045-2322
%X 
%Z FOR Codes: 111201


%0 Journal Article
%~ PubMed
%A Hilton, H N
%A Kalyuga, M
%A Cowley, M J
%A Alles, M C
%A Lee, H J
%A Caldon, C E
%A Blazek, K
%A Kaplan, W
%A Musgrove, E A
%A Daly, R J
%A Naylor, M J
%A Graham, J D
%A Clarke, C L
%A Ormandy, C J
%T The Antiproliferative Effects of Progestins in T47D Breast Cancer Cells Are Tempered by Progestin Induction of the ETS Transcription Factor Elf5.
%B Molecular Endocrinology
%D 2010
%C United States
%I The Endocrine Society
%V 24
%N 7
%P 1380-1392
%@ 1944-9917
%X Prolactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induced by progestins in breast cancer cells via a direct mechanism. To define the transcriptional response to progestin elicited via Elf5, we made an inducible Elf5 short hairpin-RNA knock-down model in T47D breast cancer cells and used it to prevent the progestin-induction of Elf5. Functional analysis of Affymetrix gene expression data using Gene Ontologies and Gene Set Enrichment Analysis showed enhancement of the progestin effects on cell cycle gene expression. Cell proliferation assays showed a more efficacious progestin-induced growth arrest when Elf5 was kept at baseline levels. These results showed that progestin induction of Elf5 expression tempered the antiproliferative effects of progestins in T47D cells, providing a further mechanistic link between prolactin and progestin in the regulation of mammary cell phenotype.
%Z FOR Codes: 110306 111201


%0 Journal Article
%~ PubMed
%A Rogers, Renee L
%A Van Seuningen, Isabelle
%A Gould, Jodee
%A Hertzog, Paul J
%A Naylor, Matthew J
%A Pritchard, Melanie A
%T Transcript profiling of Elf5+/- mammary glands during pregnancy identifies novel targets of Elf5.
%B PloS One
%D 2010
%C United States
%I Public Library of Science
%V 5
%N 10
%P e13150
%@ 1932-6203
%X Elf5, an epithelial specific Ets transcription factor, plays a crucial role in the pregnancy-associated development of the mouse mammary gland. Elf5(-/-) embryos do not survive, however the Elf5(+/-) mammary gland displays a severe pregnancy-associated developmental defect. While it is known that Elf5 is crucial for correct mammary development and lactation, the molecular mechanisms employed by Elf5 to exert its effects on the mammary gland are largely unknown.
%Z FOR Codes: 110306


%0 Journal Article
%~ PubMed
%A Akhtar, Nasreen
%A Marlow, Rebecca
%A Lambert, Elise
%A Schatzmann, Franziska
%A Lowe, Emma T
%A Cheung, Julia
%A Katz, Elad
%A Li, Weiping
%A Wu, Chuanyue
%A Dedhar, Shoukat
%A Naylor, Matthew J
%A Streuli, Charles H
%T Molecular dissection of integrin signalling proteins in the control of mammary epithelial development and differentiation.
%B Development
%D 2009
%C United Kingdom
%I The Company of Biologists Ltd.
%V 136
%N 6
%P 1019-1027
%@ 0950-1991
%X Cell-matrix adhesion is essential for the development and tissue-specific functions of epithelia. For example, in the mammary gland, beta1-integrin is necessary for the normal development of alveoli and for the activation of endocrine signalling pathways that determine cellular differentiation. However, the adhesion complex proteins linking integrins with downstream effectors of hormonal signalling pathways are not known. To understand the mechanisms involved in connecting adhesion with this aspect of cell phenotype, we examined the involvement of two proximal beta1-integrin signalling intermediates, integrin-linked kinase (ILK) and focal adhesion kinase (FAK). By employing genetic analysis using the Cre-LoxP system, we provide evidence that ILK, but not FAK, has a key role in lactogenesis in vivo and in the differentiation of cultured luminal epithelial cells. Conditional deletion of ILK both in vivo and in primary cell cultures resulted in defective differentiation, by preventing phosphorylation and nuclear translocation of STAT5, a transcription factor required for lactation. Expression of an activated RAC (RAS-related C3 botulinum substrate) in ILK-null acini restored the lactation defect, indicating that RAC1 provides a mechanistic link between the integrin/ILK adhesion complex and the differentiation pathway. Thus, we have determined that ILK is an essential downstream component of integrin signalling involved in differentiation, and have identified a high degree of specificity within the integrin-based adhesome that links cell-matrix interactions with the tissue-specific function of epithelia.
%Z FOR Codes: 110106


%0 Journal Article
%~ PubMed
%A Oakes, Samantha R
%A Rogers, Renee L
%A Naylor, Matthew J
%A Ormandy, Christopher J
%T Prolactin regulation of mammary gland development.
%B Journal of Mammary Gland Biology and Neoplasia
%D 2008
%C United States
%I Springer New York LLC
%V 13
%N 1
%P 13-28
%@ 1573-7039
%X Mammary morphogenesis is orchestrated with other reproductive events by pituitary-driven changes to the systemic hormone environment, initiating the formation of a mammary ductal network during puberty and the addition of secretory alveoli during pregnancy. Prolactin is the major driver of development during pregnancy via regulation of ovarian progesterone production (in many species) and direct effects on mammary epithelial cells (in all species). Together these hormones regulate two aspects of development that are the subject of intense interest: (1) a genomic regulatory network that integrates many additional spatial and temporal cues to control gene expression and (2), the activity of a stem and progenitor cell hierarchy. Amalgamation of these two aspects will increase our understanding of cell proliferation and differentiation within the mammary gland, with clear application to our attempts to control breast cancer. Here we focus on providing an over-view of prolactin action during development of the model murine mammary gland.
%Z FOR Codes: 601


%0 Journal Article
%~ PubMed
%A Oakes, Samantha R
%A Naylor, Matthew J
%A Asselin-Labat, Marie-Liesse
%A Blazek, Katrina D
%A Gardiner-Garden, Margaret
%A Hilton, Heidi N
%A Kazlauskas, Michael
%A Pritchard, Melanie A
%A Chodosh, Lewis A
%A Pfeffer, Peter L
%A Lindeman, Geoffrey J
%A Visvader, Jane E
%A Ormandy, Christopher J
%T The Ets transcription factor Elf5 specifies mammary alveolar cell fate.
%B Genes & Development
%D 2008
%C United States
%I Cold Spring Harbor Laboratory Press
%V 22
%N 5
%P 581-586
%@ 0890-9369
%X Hormonal cues regulate mammary development, but the consequent transcriptional changes and cell fate decisions are largely undefined. We show that knockout of the prolactin-regulated Ets transcription factor Elf5 prevented formation of the secretory epithelium during pregnancy. Conversely, overexpression of Elf5 in an inducible transgenic model caused alveolar differentiation and milk secretion in virgin mice, disrupting ductal morphogenesis. CD61+ luminal progenitor cells accumulated in Elf5-deficient mammary glands and were diminished in glands with Elf5 overexpression. Thus Elf5 specifies the differentiation of CD61+ progenitors to establish the secretory alveolar lineage during pregnancy, providing a link between prolactin, transcriptional events, and alveolar development.
%Z FOR Codes: 60403


%0 Journal Article
%~ PubMed
%A Naylor, Matthew J
%A Ormandy, Christopher J
%T Gata-3 and mammary cell fate.
%B Breast Cancer Research
%D 2007
%C United Kingdom
%I BioMed Central Ltd.
%V 9
%N 2
%P 302
%@ 1465-542X
%X Genomic regulatory networks specify how cellular gene expression responds to external temporal and spatial stimuli, ensuring that correct cell fate decisions are made and the appropriate cell phenotypes are adopted. In mammary epithelial cells, the hierarchy of stem and progenitor cells and the genetically specified program of transcriptional activity are beginning to be elucidated and integrated. A novel role for Gata-3 in specifying and maintaining mammary cell fate has recently been identified. These reports offer an understanding of how mammary cells assume and maintain a variety of cell behaviours and functions, and how a mammary cell may potentially subvert these constraints during carcinogenesis.
%Z FOR Codes: 111203


%0 Book Section
%A Naylor, Matthew
%A Streuli, Charles H.
%T Integrin Regulation of Mammary Gland Development
%B Integrins and Development
%D 2006
%C United States
%I Landes Bioscience
%V 
%N 
%P 176-185
%@ 9781587062933
%E Danen, Erik H.J.
%X 
%Z FOR Codes: 1116


%0 Journal Article
%~ PubMed
%A Harris, Jessica
%A Stanford, Prudence M
%A Sutherland, Kate
%A Oakes, Samantha R
%A Naylor, Matthew J
%A Robertson, Fiona G
%A Blazek, Katrina D
%A Kazlauskas, Michael
%A Hilton, Heidi N
%A Wittlin, Sergio
%A Alexander, Warren S
%A Lindeman, Geoffrey J
%A Visvader, Jane E
%A Ormandy, Christopher J
%T Socs2 and elf5 mediate prolactin-induced mammary gland development.
%B Molecular Endocrinology
%D 2006
%C United States
%I The Endocrine Society
%V 20
%N 5
%P 1177-1187
%@ 0888-8809
%X The proliferative phase of mammary alveolar morphogenesis is initiated during early pregnancy by rising levels of serum prolactin and progesterone, establishing a program of gene expression that is ultimately responsible for the development of the lobuloalveoli and the onset of lactation. To explore this largely unknown genetic program, we constructed transcript profiles derived from transplanted mammary glands formed by recombination of prolactin receptor (Prlr) knockout or wild-type mammary epithelium with wild-type mammary stroma. Comparison with profiles derived from prolactin-treated Scp2 mammary epithelial cells produced a small set of commonly prolactin-regulated genes that included the negative regulator of cytokine signaling, Socs2 (suppressor of cytokine signaling 2), and the ets transcription factor, E74-like factor 5 (Elf5). Homozygous null mutation of Socs2 rescued the failure of lactation and reduction of mammary signal transducer and activator of transcription 5 phosphorylation that characterizes Prlr heterozygous mice, demonstrating that mammary Socs2 is a key regulator of the prolactin-signaling pathway. Reexpression of Elf5 in Prlr nullizygous mammary epithelium restored lobuloalveolar development and milk production, demonstrating that Elf5 is a transcription factor capable of substituting for prolactin signaling. Thus, Socs2 and Elf5 are key members of the set of prolactin-regulated genes that mediate prolactin-driven mammary development.
%Z FOR Codes: 30405 110306