title: Models of breast morphogenesis based on localization of stem cells in the developing mammary lobule.
abstract: Characterization of normal breast stem cells is important for understanding their role in breast development and in breast cancer. However, the identity of these cells is a subject of controversy and their localization in the breast epithelium is not known. In this study, we utilized a novel approach to analyze the morphogenesis of mammary lobules, by combining one-dimensional theoretical models and computer-generated 3D fractals. Comparing predictions of these models with immunohistochemical analysis of tissue sections for candidate stem cell markers, we defined distinct areas where stem cells reside in the mammary lobule. An increased representation of stem cells was found in smaller, less developed lobules compared to larger, more mature lobules, with marked differences in the gland of nulliparous versus parous women and that of BRCA1/2 mutation carriers versus non-carriers.
authors.affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK. Electronic address: gabriella.honeth@med.lu.se.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Honeth
authors.affiliation: U-Hopper s.r.l., Trento 38123, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Schiavinotto
authors.affiliation: Department of Computational Biology, Research and Innovation Centre-Fondazione Edmund Mach, San Michele all'Adige 38010, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Vaggi
authors.affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK; Breakthrough Breast Cancer Research Unit, King's College London School of Medicine, London SE1 9RT, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Marlow
authors.affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK.
authors.forename: Tokuwa
authors.initials: T
authors.lastname: Kanno
authors.affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK.
authors.forename: Ireneusz
authors.initials: I
authors.lastname: Shinomiya
authors.affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Lombardi
authors.affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK; Breakthrough Breast Cancer Research Unit, King's College London School of Medicine, London SE1 9RT, UK.
authors.forename: Bharath
authors.initials: B
authors.lastname: Buchupalli
authors.affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Graham
authors.affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Gazinska
authors.affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK.
authors.forename: Vernie
authors.initials: V
authors.lastname: Ramalingam
authors.affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK.
authors.forename: Joy
authors.initials: J
authors.lastname: Burchell
authors.affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK.
authors.forename: Anand D
authors.initials: AD
authors.lastname: Purushotham
authors.affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Pinder
authors.affiliation: Department of Computational Biology, Research and Innovation Centre-Fondazione Edmund Mach, San Michele all'Adige 38010, Italy; Randall Division of Cell and Molecular Biophysics and Institute of Mathematical and Molecular Biomedicine, King's College London, London SE1 1UL, UK.
authors.forename: Attila
authors.initials: A
authors.lastname: Csikasz-Nagy
authors.affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK. Electronic address: gabriela.dontu@kcl.ac.uk.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Dontu
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human; D008954:Models, Biological; D038081:Organogenesis; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: D015415:Biomarkers
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