Key signalling nodes in mammary gland development and cancer. Mitogen-activated protein kinase signalling in experimental models of breast cancer progression and in mammary gland development

Seven classes of mitogen-activated protein kinase (MAPK) intracellular signalling cascades exist, four of which are implicated in breast disease and function in mammary epithelial cells. These are the extracellular regulated kinase (ERK)1/2 pathway, the ERK5 pathway, the p38 pathway and the c-Jun N-terminal kinase (JNK) pathway. In some forms of human breast cancer and in many experimental models of breast cancer progression, signalling through the ERK1/2 pathway, in particular, has been implicated as being important. We review the influence of ERK1/2 activity on the organised three-dimensional association of mammary epithelial cells, and in models of breast cancer cell invasion. We assess the importance of epidermal growth factor receptor family signalling through ERK1/2 in models of breast cancer progression and the influence of ERK1/2 on its substrate, the oestrogen receptor, in this context. In parallel, we consider the importance of these MAPK-centred signalling cascades during the cycle of mammary gland development. Although less extensively studied, we highlight the instances of signalling through the p38, JNK and ERK5 pathways involved in breast cancer progression and mammary gland development

The Cosmonauts challenge

Focusing on the experience of working with Russia’s cultural, industrial and political sectors, this paper investigates how the development of new contacts and partnerships has contributed not only to the loan of material of historic significance to the Science Museum’s exhibition, but more broadly changes perceptions about Russia and its space programme in the western world. Addressing the multiple challenges involved – legal, political and security, among others – it reveals the importance of many of the space objects themselves as well as demonstrating how the Science Museum has helped to maintain a dialogue with Russia even during the most testing times. In September 2015 the Science Museum opened the most ambitious special exhibition it had ever undertaken: Cosmonauts: birth of the space age. Whilst the creation of a ‘blockbuster’ exhibition might be the normal expectation of a great art museum, the fact that a science museum should undertake such an endeavour is equally worthy of comment, and this article seeks to illustrate the exceptional curatorial, museological, logistical, legal and political hurdles that this project had to overcome. Indeed, they would astonish even the grandest and most experienced of the international art museums. Art museums are delighted when they can display the acclaimed works of Monet, but even the most valuable paintings cannot be said to be have been official state secrets in the way that so much Russian space technology has been. The curatorial team kept its nerve because of a compelling sense that while the project delivery was high stress, the intellectual rewards would be considerable, and especially the opportunity to present a story of human endeavour in which cultural and scientific excellence are so intertwined. When the project team started out they could never have anticipated that they would be seeking to deliver an audacious exhibition set against a background of very serious strains in the UK-Russia relationship. In the end, they learned a great deal about Russia itself and the importance of sustaining cultural dialogue

Method for the generation and cultivation of functional three-dimensional mammary constructs without exogenous extracellular matrix

During puberty, pregnancy, lactation and postlactation, breast tissue undergoes extensive remodelling and the disruption of these events can lead to cancer. In vitro studies of mammary tissue and its malignant transformation regularly employ mammary epithelial cells cultivated on matrigel or floating collagen rafts. In these cultures, mammary epithelial cells assemble into three-dimensional structures resembling in vivo acini. We present a novel technique for generating functional mammary constructs without the use of matrix substitutes

Expression Pattern of the Pro-apoptotic Gene PAR-4 During the Morphogenesis of MCF-10A Human Mammary Epithelial Cells

The histological organization of the mammary gland involves a spatial interaction of epithelial and myoepithelial cells with the specialized basement membrane (BM), composed of extra-cellular matrix (ECM) proteins, which is disrupted during the tumorigenic process. The interactions between mammary epithelial cells and ECM components play a major role in mammary gland branching morphogenesis. Critical signals for mammary epithelial cell proliferation, differentiation, and survival are provided by the ECM proteins. Three-dimensional (3D) cell culture was developed to establish a system that simulates several features of the breast epithelium in vivo; 3D cell culture of the spontaneously immortalized cell line, MCF10A, is a well-established model system to study breast epithelial cell biology and morphogenesis. Mammary epithelial cells grown in 3D form spheroids, acquire apicobasal polarization, and form lumens that resemble acini structures, processes that involve cell death. Using this system, we evaluated the expression of the pro-apoptotic gene PAWR (PKC apoptosis WT1 regulator; also named PAR-4, prostate apoptosis response-4) by immunofluorescence and quantitative real time PCR (qPCR). A time-dependent increase in PAR-4 mRNA expression was found during the process of MCF10A acinar morphogenesis. Confocal microscopy analysis also showed that PAR-4 protein was highly expressed in the MCF10A cells inside the acini structure. During the morphogenesis of MCF10A cells in 3D cell culture, the cells within the lumen showed caspase-3 activation, indicating apoptotic activity. PAR-4 was only partially co-expressed with activated caspase-3 on these cells. Our results provide evidence, for the first time, that PAR-4 is differentially expressed during the process of MCF10A acinar morphogenesis

Correlates of gross motor competence in children and adolescents: A systematic review and meta-analysis

Background Gross motor competence confers health benefits, but levels in children and adolescents are low. While interventions can improve gross motor competence, it remains unclear which correlates should be targeted to ensure interventions are most effective, and for whom targeted and tailored interventions should be developed. Objective The aim of this systematic review was to identify the potential correlates of gross motor competence in typically developing children and adolescents (aged 3–18 years) using an ecological approach. Methods Motor competence was defined as gross motor skill competency, encompassing fundamental movement skills and motor coordination, but excluding motor fitness. Studies needed to assess a summary score of at least one aspect of motor competence (i.e., object control, locomotor, stability, or motor coordination). A structured electronic literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Six electronic databases (CINAHL Complete, ERIC, MEDLINE Complete, PsycINFO, Scopus and SPORTDiscus with Full Text) were searched from 1994 to 5 August 2014. Meta-analyses were conducted to determine the relationship between potential correlates and motor competency if at least three individual studies investigated the same correlate and also reported standardized regression coefficients. Results A total of 59 studies were identified from 22 different countries, published between 1995 and 2014. Studies reflected the full range of age groups. The most examined correlates were biological and demographic factors. Age (increasing) was a correlate of children’s motor competence. Weight status (healthy), sex (male) and socioeconomic background (higher) were consistent correlates for certain aspects of motor competence only. Physical activity and sport participation constituted the majority of investigations in the behavioral attributes and skills category. Whilst we found physical activity to be a positive correlate of skill composite and motor coordination, we also found indeterminate evidence for physical activity being a correlate of object control or locomotor skill competence. Few studies investigated cognitive, emotional and psychological factors, cultural and social factors or physical environment factors as correlates of motor competence. Conclusion This systematic review is the first that has investigated correlates of gross motor competence in children and adolescents. A strength is that we categorized correlates according to the specific ways motor competence has been defined and operationalized (object control, motor coordination, etc.), which enables us to have an understanding of what correlates assist what types of motor competence. Indeed our findings do suggest that evidence for some correlates differs according to how motor competence is operationalized