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The Mammary Microenvironment in Mastitis in Humans, Dairy Ruminants, Rabbits and Rodents: A One Health Focus

The One Health concept promotes integrated evaluation of human, animal, and environmental health questions to expedite advances benefiting all species. A recognition of the multi-species impact of mastitis as a painful condition with welfare implications leads us to suggest that mastitis is an ideal target for a One Health approach. In this review, we will evaluate the role of...

Anti-CCL2: building a reservoir or opening the floodgates to metastasis?

Neutralisation of macrophage chemoattractant C-C chemokine ligand 2 (CCL2) has shown reduced metastasis and enhanced survival in numerous experimental models of tumorigenesis. However, important new findings reported in Nature by Momo Bentires-Alj’s laboratory demonstrate that withdrawal of anti-CCL2 treatment accelerates lung metastasis and death in mice. The study highlights...

Elf5 - breast cancer's little helper

A variety of transcription factors has been shown to regulate lineage commitment in the mammary gland and to be associated with different molecular subtypes of breast cancer. E74-like factor 5 (Elf5) has now been identified as a marker of oestrogen receptor status, and high expression correlates with more aggressive basal cancers and resistance to anti-oestrogens. Manipulation of...

A prophylactic vaccine for breast cancer?

Christine J Watson 0 Barry A Gusterson 1 0 Department of Pathology, University of Cambridge , Tennis Court Road, Cambridge CB2 1QP , UK 1 Department of Pathology, Institute of Cancer Sciences

Key signalling nodes in mammary gland development and cancer. Signalling downstream of PI3 kinase in mammary epithelium: a play in 3 Akts

The protein serine/threonine kinase Akt, also known as protein kinase B (PKB), is arguably the most important signalling nexus in the cell. Akt integrates a plethora of extracellular signals to generate diverse outcomes, including proliferation, motility, growth, glucose homeostasis, survival, and cell death. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is the second most...

Stat3 Is Required to Maintain the Full Differentiation Potential of Mammary Stem Cells and the Proliferative Potential of Mammary Luminal Progenitors

Stat3 has a defined role in mammary gland where it is a critical mediator of cell death during post-lactational regression. On the other hand, Stat3 is required for the self-renewal of embryonic stem cells and is sufficient for the induction of a naïve pluripotent state in epiblast stem cells. Mammary stem cells (MaSCs) have a high capacity for self-renewal and can grow robustly...

Key stages in mammary gland development - Involution: apoptosis and tissue remodelling that convert the mammary gland from milk factory to a quiescent organ

: Christine J Watson 0 cjw 0 0 0 Department of Pathology, University of Cambridge , Tennis Court Road, Cambridge CB2 1QP , UK Involution of the mammary gland is an essential process that

A Multifunctional 3D Co-Culture System for Studies of Mammary Tissue Morphogenesis and Stem Cell Biology

Studies on the stem cell niche and the efficacy of cancer therapeutics require complex multicellular structures and interactions between different cell types and extracellular matrix (ECM) in three dimensional (3D) space. We have engineered a 3D in vitro model of mammary gland that encompasses a defined, porous collagen/hyaluronic acid (HA) scaffold forming a physiologically...

Mammary development in the embryo and adult: a journey of morphogenesis and commitment

Christine J. Watson 0 Walid T. Khaled 0 0 Department of Pathology, University of Cambridge , Tennis Court Road, Cambridge CB2 1QP, UK Mammary gland development occurs through distinctive stages

Phenotypic and functional characterisation of the luminal cell hierarchy of the mammary gland

Introduction The organisation of the mammary epithelial hierarchy is poorly understood. Our hypothesis is that the luminal cell compartment is more complex than initially described, and that an understanding of the developmental relationships within this lineage will help in understanding the cellular context in which breast tumours occur. Methods We used fluorescence-activated...

Postpartum Remodeling, Lactation, and Breast Cancer Risk: Summary of a National Cancer Institute–Sponsored Workshop

0 Christine J. Watson 0 Mark E. Sherman ) 0 0 Epidemiology Branch , 6120 Executive Blvd, Rm 5028, Rockville, MD 20852-7234 ( The pregnancy-lactation cycle (PLC) is a period in which the breast is

Caspase-dependent proteolytic cleavage of STAT3α in ES cells, in mammary glands undergoing forced involution and in breast cancer cell lines

Background The STAT (Signal Transducers and Activators of Transcription) transcription factor family mediates cellular responses to a wide range of cytokines. Activated STATs (particularly STAT3) are found in a range of cancers. Further, STAT3 has anti-apoptotic functions in a range of tumour cell lines. After observing a proteolytic cleavage in STAT3α close to a potential...

Characterisation of microRNA expression in post-natal mouse mammary gland development

Background The differential expression pattern of microRNAs (miRNAs) during mammary gland development might provide insights into their role in regulating the homeostasis of the mammary epithelium. Our aim was to analyse these regulatory functions by deriving a comprehensive tissue-specific combined miRNA and mRNA expression profile of post-natal mouse mammary gland development...

IKKβ/2 induces TWEAK and apoptosis in mammary epithelial cells

Fiona O. Baxter Paul J. Came Kathrine Abell Blandine Kedjouar Marion Huth Klaus Rajewsky Manolis Pasparakis Christine J. Watson The Nuclear Factor- B (NF- B) family of transcription factors are

Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression

Introduction In order to gain a better understanding of the molecular processes that underlie apoptosis and tissue regression in mammary gland, we undertook a large-scale analysis of transcriptional changes during the mouse mammary pregnancy cycle, with emphasis on the transition from lactation to involution. Method Affymetrix microarrays, representing 8618 genes, were used to...

The IL-4/IL-13/Stat6 signalling pathway promotes luminal mammary epithelial cell development

. Came 0 Naomi Sprigg Andrew N. J. McKenzie Christine J. Watson 0 Present address: Faculty of Life Sciences, University of Manchester , Oxford Road, Manchester, M13 9PT , UK Naïve T helper cells

Identification and characterisation of a developmentally regulated mammalian gene that utilises –1 programmed ribosomal frameshifting

Translational recoding of mRNA through a –1 ribosomal slippage mechanism has been observed in RNA viruses and retrotransposons of both eukaryotes and prokaryotes. Whilst this provides a potentially powerful mechanism of gene regulation, the utilization of –1 translational frameshifting in regulating mammalian gene expression has remained obscure. Here we report a mammalian gene...

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

Introduction Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. Methods More than 100 internationally recognised specialist breast cancer scientists, clinicians and...