Hennighausen L, Robinson GW.. Information networks in the mammary gland. Nat Rev Mol Cell Biol 6: 715-725

Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature Reviews Molecular Cell Biology (Impact Factor: 37.81). 10/2005; 6(9):715-25. DOI: 10.1038/nrm1714
Source: PubMed


Unique developmental features during puberty, pregnancy, lactation and post-lactation make the mammary gland a prime object to explore genetic circuits that control the specification, proliferation, differentiation, survival and death of cells. Steroids and simple peptide hormones initiate and carry out complex developmental programmes, and reverse genetics has been used to define the underlying mechanistic connections.

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    • "During pregnancy, the gland undergoes another period of rapid differentiation, involving branching and the development of lobulo-alveoli to prepare for lactation [19]. Male breast development also occurs in utero, but the androgen surge halts further development immediately prior to birth. "
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    ABSTRACT: Although understanding the environmental factors that contribute to breast cancer could improve disease prevention, standard chemical testing protocols do not adequately evaluate chemicals' effects on breast development. Evidence suggests: (1) Mammary gland (MG) development is a complex process that extends from gestation through fetal and neonatal growth, puberty, and pregnancy; (2) altered MG development can increase the risk of breast cancer and other adverse outcomes; and (3) chemical exposures during susceptible windows of development may alter the MG in ways that increase risk for later disease. Together, these highlight the need to better understand the complex relationship between exposure to endocrine disrupting compounds (EDCs) and the alterations in MG morphology and gene expression that ultimately increase disease risk. Changing guideline toxicity testing studies to incorporate perinatal exposures and MG whole mounts would generate critical knowledge about the effects of EDCs on the MG and could ultimately inform disease prevention.
    Reproductive Toxicology 08/2014; 378. DOI:10.1016/j.reprotox.2014.07.077 · 3.23 Impact Factor
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    • "In adult nulliparous females, the mammary gland is mostly populated by adipocytes with the embedded epithelial network [1], [2]. Gestation initiates massive proliferation of the progenitor cells to form lobuloalveolar structures which will ultimately differentiate to milk secreting glandular epithelium upon parturition [3]–[5]. Cessation of suckling triggers a drop in lactogenic hormones and heralds the necessity for the involution. "
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    ABSTRACT: The post-lactational regression of mammary gland is a complex multi-step process designed to conserve the biological function of the gland for next pregnancy. This developmental stage is a biological intrigue with great relevance to breast cancer research, and thus has been the subject of intensive scrutiny. Multipronged studies (microarray, proteomics profiling, animal knock-out models) have provided a repertoire of genes critical to involution. However, the caveat of these approaches remains in their failure to reveal post-translational modification(s), an emerging and critical aspect of gene regulation in developmental processes and mammary gland remodeling. The massive surge in the lysosomal enzymes concurrent with the onset of involution has been known for decades, and considered essential for "clearance" purposes. However, functional significance of these enzymes in diverse biological processes distinct from their proteolytic activity is just emerging. Studies from our laboratory had indicated specific post-translational modifications of the aspartyl endopeptidase Cathepsin D (CatD) at distinct stages mammary gland development. This study addresses the biological significance of these modifications in the involution process, and reveals that post-translational modifications drive CatD into the nucleus to cleave Histone 3. The cleavage of Histone 3 has been associated with cellular differentiation and could be critical instigator of involution process. From functional perspective, deregulated expression and increased secretion of CatD are associated with aggressive and metastatic phenotype of breast cancer. Thus unraveling CatD's physiological functions in mammary gland development will bridge the present gap in understanding its pro-tumorigenic/metastatic functions, and assist in the generation of tailored therapeutic approaches.
    PLoS ONE 07/2014; 9(7):e103230. DOI:10.1371/journal.pone.0103230 · 3.23 Impact Factor
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    • "The requirement of gelsolin for ductal development of the mammary epithelium is not surprising. Gelsolin mediates epidermal growth factor (EGF) effects on cell motility [35] and EGF controls ductal outgrowth, elongation and branching [36], [37]. The present study shows enhanced expression of gelsolin during peak stage of lactation. "
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    ABSTRACT: Mammary gland is made up of a branching network of ducts that end with alveoli which surrounds the lumen. These alveolar mammary epithelial cells (MEC) reflect the milk producing ability of farm animals. In this study, we have used 2D-DIGE and mass spectrometry to identify the protein changes in MEC during immediate early, peak and late stages of lactation and also compared differentially expressed proteins in MEC isolated from milk of high and low milk producing cows. We have identified 41 differentially expressed proteins during lactation stages and 22 proteins in high and low milk yielding cows. Bioinformatics analysis showed that a majority of the differentially expressed proteins are associated in metabolic process, catalytic and binding activity. The differentially expressed proteins were mapped to the available biological pathways and networks involved in lactation. The proteins up-regulated during late stage of lactation are associated with NF-κB stress induced signaling pathways and whereas Akt, PI3K and p38/MAPK signaling pathways are associated with high milk production mediated through insulin hormone signaling.
    PLoS ONE 07/2014; 9(8):e102515. DOI:10.1371/journal.pone.0102515 · 3.23 Impact Factor
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