DOCSLIB.ORG

Unraveling Heterogeneity in Epithelial Cell Fates of the Mammary Gland and Breast Cancer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Unraveling Heterogeneity in Epithelial Cell Fates of the Mammary Gland and Breast Cancer cancers Review Unraveling Heterogeneity in Epithelial Cell Fates of the Mammary Gland and Breast Cancer 1, 1 2 1, Alexandr Samocha y, Hanna Doh , Kai Kessenbrock and Jeroen P. Roose * 1 Department of Anatomy, University of California, San Francisco, CA 94143, USA; [email protected] (A.S.); [email protected] (H.D.) 2 Department of Biological Chemistry, University of California, Irvine, CA 92697, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-415-476-3977 Current address: Wild Type, Inc. 953 Indiana Street, San Francisco, CA 94107, USA. y Received: 21 August 2019; Accepted: 22 September 2019; Published: 24 September 2019 Abstract: Fluidity in cell fate or heterogeneity in cell identity is an interesting cell biological phenomenon, which at the same time poses a significant obstacle for cancer therapy. The mammary gland seems a relatively straightforward organ with stromal cells and basal- and luminal- epithelial cell types. In reality, the epithelial cell fates are much more complex and heterogeneous, which is the topic of this review. Part of the complexity comes from the dynamic nature of this organ: the primitive epithelial tree undergoes extensively remodeling and expansion during puberty, pregnancy, and lactation and, unlike most other organs, the bulk of mammary gland development occurs late, during puberty. An active cell biological debate has focused on lineage commitment to basal- and luminal- epithelial cell fates by epithelial progenitor and stem cells; processes that are also relevant to cancer biology. In this review, we discuss the current understanding of heterogeneity in mammary gland and recent insights obtained through lineage tracing, signaling assays, and organoid cultures. Lastly, we relate these insights to cancer and ongoing efforts to resolve heterogeneity in breast cancer with single-cell RNAseq approaches. Keywords: mammary gland; breast cancer; cell fate; heterogeneity; 3D cultures; organoids; signaling; single-cell RNAseq 1. Introduction into Mammary Gland Structure, Function and Early Development The mammary gland is comprised of many different interacting cell types. Epithelial cells form a primitive structure early during embryonic development, which later form the nipple and a ductal network that expands into the fat pad. These epithelial ducts are surrounded by fat cells, and become innervated with a variety of stromal cells including endothelial cells, immune cells, and fibroblasts [1]. Maturation of the gland is regulated at first by mesenchymal interactions, and later by hormone and growth factor receptor signaling during puberty and pregnancy. Mammary epithelial cells assemble into their normal morphology between E16-E18 (embryonic day), forming a bilayered duct with an inner lumen [2]. Together, the mammary epithelial subtypes interact to carry out the organ’s functions. After pregnancy, mature epithelial cells can later differentiate into alveolar cells and subsequently produce milk proteins. Mammary epithelial cells (MECs) typically form a bilayered epithelium and can be broadly separated into two distinct compartments: an inner layer of luminal and outer layer of basal MECs. However, additional heterogeneity exists within both luminal and basal MECs. Luminal populations are often sub classified based on hormone and growth factor receptor status. The basal epithelium contains a subset of so-called myoepithelial cells that lie along the outside of the ductal epithelial tree Cancers 2019, 11, 1423; doi:10.3390/cancers11101423 www.mdpi.com/journal/cancers Cancers 2019, 11, x 2 of 19 Cancers 2019, 11, 1423 2 of 19 and assist in the motility of milk protein along the lumen. The MEC system also contains subsets of basal and luminal stem and progenitor cells, which will be covered in greater detail later. For andexample, assist within in the the motility luminal of milk compartment protein along a population the lumen. of luminal The MEC progenitor system also cells contains can go on subsets to form of basalductal and or luminalalveolar stem cells. and In progenitoraddition, basal cells, cell whichs contain will be a covered subset inof greatermammary detail stem later. cells For example,(MaSCs) withinforming the a luminalsmall, heterogeneous, compartment aand population to date poor of luminally defined progenitor population cells canthat godrive on todevelopment, form ductal orrepair alveolar and organ cells. Inreconstitution addition, basal when cells transplanted contain a subset into epithelium-cleared of mammary stem fat cells pads (MaSCs) of recipient forming mice a small,[3]. heterogeneous, and to date poorly defined population that drive development, repair and organ reconstitutionPuberty is when the most transplanted dynamic into and epithelium-cleared striking period during fat pads the of development recipient mice of [3 ].the mammary gland.Puberty The rudimentary is the most duct dynamic undergoes and strikingsignificant period expansion, during resulting the development in the formation of the of mammary bulbous gland.multilayered The rudimentary structures ductcalled undergoes terminal end significant buds (TEBs) expansion, [4] (Figure resulting 1). in TEBs the formationare the proliferative of bulbous multilayeredcenters that drive structures elongation, called bifurcation, terminal end and buds branching (TEBs) until [4] (Figure the entirety1). TEBs of the are mammary the proliferative fat pad centersis filled, that thereby drive creating elongation, the mature bifurcation, epithelial andbranching tree [5]. The until TEB the contains entirety cap of thecells, mammary a rapidly fat growing pad is filled,and dividing thereby progenitor creating the cell mature popula epithelialtion that tree later [5 ].goes The on TEB to form contains the captree’s cells, outer a rapidly myoepithelial growing layer and dividing[6]. progenitor cell population that later goes on to form the tree’s outer myoepithelial layer [6]. Figure 1.1. Schematic of mouse mammary gland developmentdevelopment during puberty. During puberty, the rudimentary ductduct undergoes undergoes significant significant expansion, expansion, resulting resulting in the formation in the offormation bulbous multilayeredof bulbous structuresmultilayered called structures terminal called end buds terminal (TEBs). end These buds TEBs (TEB ares). theThese proliferative TEBs are the centers proliferative that drive centers elongation, that bifurcation,drive elongation, and branching bifurcation, of ducts and untilbranching the entirety of ducts of theuntil mammary the entirety fatpad of the is filled, mammary thereby fat creating pad is thefilled, mature thereby epithelial creating tree. the mature epithelial tree. 2. Luminal Cells and Lumi Luminal-Specificnal-Specific ProgenitorsProgenitors The luminalluminal compartment compartment contains contains diff erentdifferent mature, ma diture,fferentiated differentiated cell populations cell populations with specified with functionsspecified functions as well as as progenitor-cell well as progenitor-cell populations populations that are that each are distinguished each distinguished by specific by specific gene gene and extracellularand extracellular ligand ligand profiles. profiles. Several classificationsclassifications of luminalluminal cellscells existexist withinwithin thethe mammarymammary gland.gland. Luminal cells are segregated based on functional,functional, morphological,morphological, andand expression profilingprofiling evidence.evidence. Histologically, Histologically, luminal cells cells can can be be broadly broadly separated separated into intotwo types: two types: ductal and ductal alveolar. and alveolar.Mature ductal Mature cells ductalcan be cellseither can estrogen be either receptor estrogen (ER) receptor positive (ER) or nega positivetive, orand negative, feature andthe featurefollowing the marker following expression marker lo lo + hi + expressionprofile: CD49f profile:loCD29 CD49floCD24+CD29CD14−EpCAMCD24 CD14hic-kit−−EpCAMSca1+CD61c-kit−CD49b−Sca1− [7],CD61 in which−CD49b the− [CD7], innumbers which theand CDother numbers markers and represent other markersdifferent representgene products. different Mature gene alveolar products. cells Mature are always alveolar estrogen cells arereceptor always (ER) estrogen negative receptor and (ER) negativecan be andmore can beprecisely more precisely characterized characterized through through a lo lo + hi lo aCD49f CD49floCD29CD29loCD24CD24+CD14CD14−EpCAM−EpCAMhiSca1loSca1CD61CD61− expression− expression pattern. pattern. Alveolar Alveolar cells cells can can be distinguished by by their their secretory secretory morphology morphology and andhistologically histologically by the by accumulation the accumulation of milk proteins of milk proteinswithin. within. Transcription factorsfactors havehave been demonstrated to drive luminal cell fate commitment throughout development. The The Elf5 (E74-like factor 5) transcription factor is one of the major drivers of luminal cell specification specification and and differentiation. differentiation. Elf5 Elf5 is able is ableto directly to directly repress repress Slug (Zinc Slug Finger (Zinc Protein Finger SNAI2) Protein SNAI2)transcription, transcription, thereby thereby blocking blocking basal basalcell determination cell determination and andpromoting promoting luminal luminal cell cell fate fate [8,9]. [8,9]. Progesterone actsacts on on mature, mature, progesterone progesterone receptor-positive receptor-positive cells andcells induces and induces expression
Load more

Recommended publications
  • Anatomy of the Human Mammary Gland: Current Status of Knowledge
    Clinical Anatomy 00:000–000 (2012) REVIEW Anatomy of the Human Mammary Gland: Current Status of Knowledge 1,2 1 FOTEINI HASSIOTOU AND DONNA GEDDES * 1Hartmann Human Lactation Research Group, School of Chemistry and Biochemistry, Faculty of Science, The University of Western Australia, Crawley, Western Australia, Australia 2School of Anatomy, Physiology and Human Biology, Faculty of Science, The University of Western Australia, Crawley, Western Australia, Australia Mammary glands are unique to mammals, with the specific function of synthe- sizing, secreting, and delivering milk to the newborn. Given this function, it is only during a pregnancy/lactation cycle that the gland reaches a mature devel- opmental state via hormonal influences at the cellular level that effect drastic modifications in the micro- and macro-anatomy of the gland, resulting in remodeling of the gland into a milk-secretory organ. Pubertal and post-puber- tal development of the breast in females aids in preparing it to assume a func- tional state during pregnancy and lactation. Remarkably, this organ has the capacity to regress to a resting state upon cessation of lactation, and then undergo the same cycle of expansion and regression again in subsequent pregnancies during reproductive life. This plasticity suggests tight hormonal regulation, which is paramount for the normal function of the gland. This review presents the current status of knowledge of the normal macro- and micro-anatomy of the human mammary gland and the distinct changes it undergoes during the key developmental stages that characterize it, from em- bryonic life through to post-menopausal age. In addition, it discusses recent advances in our understanding of the normal function of the breast during lac- tation, with special reference to breastmilk, its composition, and how it can be utilized as a tool to advance knowledge on normal and aberrant breast devel- opment and function.
    [Show full text]
  • Implications of Breastfeeding in Triple Negative Breast Cancer THESIS
    Implications of Breastfeeding in Triple Negative Breast Cancer THESIS Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Mustafa M. Basree Graduate Program in Anatomy The Ohio State University 2017 Thesis Committee: Bhuvaneswari Ramaswamy, MD MRCP, Research Advisor Gustavo Leone, PhD, Research Advisor Eileen Kalmar, PhD, Academic Advisor Sarmila Majumder, PhD Kirk McHugh, PhD Copyright by Mustafa M. Basree 2017 Abstract Due to high mortality associated with triple negative breast cancer (TNBC), a prevention program has the potential to protect many women against this disease. Recent epidemiological and meta-analysis studies revealed a possible correlation between a lack of breastfeeding and development of TNBC. African-American (AA) women have a disproportionate burden of developing aggressive TNBC, a sub-population with higher parity rates and lower prevalence of breastfeeding. The reasons for why parity and breastfeeding affect breast cancer risk are unclear, but recent studies revealed that the pregnancy-lactation cycle (which leads to remodeling of the mammary glands) alters breast morphology and microenvironment, thereby modifying breast cancer risk. Natural weaning (NW), the gradual cessation of breastfeeding, results in a measured reduction of the ductal structures, termed involution. Conversely, the decision not to breastfeed results in a hastened involution, or abrupt involution (AW). We modeled NW and AW in wild- type mice by restricting breastfeeding to 28 and 7 days respectively. Striking differences in the distribution of cell populations were observed in the mammary glands of AW mice compared to NW mice. Fluorescence activated cell sorting analysis revealed an expansion of the luminal progenitor cells with a concomitant decrease in mammary stem- cell enriched/basal compartment in the glands of the AW cohort.
    [Show full text]
  • Basement Membrane Protein Laminin Alpha-5 in Mammary Gland Development
    Hanne Cojoc BASEMENT MEMBRANE PROTEIN LAMININ ALPHA-5 IN MAMMARY GLAND DEVELOPMENT Faculty of Biomedical Sciences Master of Science Thesis February 2020 i ABSTRACT Hanne Cojoc: Basement membrane protein laminin alpha-5 in mammary gland development Master of Science Thesis Tampere University Master’s Degree Programme in Bioengineering February 2020 The mammary gland is a special structure that differentiates mammals from other animals. It also differs from other organs by the fact that much of mammary gland development occurs post- natally during puberty and pregnancy. The dynamic structure of the mammary gland changes with age, menstrual cycle, and reproductive status in the female, with the main function being lactation, or secretion of milk for the nourishment of the offspring. The aim of this Master’s thesis was to investigate the role of basement membrane protein laminin alpha-5 (LMα5) in mammary gland development. Basement membranes can be found in almost all metazoan tissue types. In the mammary gland the basement membrane lies beneath the mammary epithelium, providing support and physiological cues for the epithelial tree. Lam- inins are a major constituent of the basement membrane, where they play a key role in several biological functions, including organ development. Laminins are deposited into the basement membrane by cells attached to it. The mammary epithelium consists of 2 types of cells; luminal epithelial cells and basal epithelial cells. Luminal epithelial cells are not adjacent to the basement membrane, but are still mostly in charge of LMα5 deposition. Due to this intriguing fact, a mice model with a conditional knockout of the LMα5 gene in luminal cells was crossed to research the protein’s role in the development of the mammary gland.
    [Show full text]
  • Study of Histology of Mammary Gland-Various Ages
    STUDY OF HISTOLOGY OF MAMMARY GLAND-VARIOUS AGES Dissertation Submitted for M.D DEGREE BRANCH - V [ANATOMY] DEPARTMENT OF ANATOMY THANJAVUR MEDICAL COLLEGE, THANJAVUR THE TAMILNADU DR.MGR MEDICAL UNIVERSITY, CHENNAI APRIL - 2015 CERTIFICATE This is to certify that dissertation titled “ STUDY OF HISTOLOGY OF MAMMARY GLAND - VARIOUS AGES” is a bonafide work done by Dr.K.ARUNA under my guidance and supervision in the Department of Anatomy, Thanjavur Medical College, Thanjavur during her post graduate course from 2012 to 2015. (Dr.K. MAHADEVAN.M.S) (Dr. T.SIVAKAMI. M.S) THE DEAN Professor and Head of the Department Thanjavur Medical College Department of Anatomy, Thanjavur-4 Thanjavur Medical College, Thanjavur-4 . DECLARATION I, Dr.K.ARUNA hereby solemnly declare that the dissertation title “STUDY OF HISTOLOGY OF MAMMARY GLAND – VARIOUS AGES”was done by me at Thanjavur Medical College and Hospital, Thanjavur under the Supervision and Guidance of my Professor and Head of the Department Dr.T.Sivakami.M.S., This dissertation is submitted to Tamil Nadu Dr. M.G.R Medical University, towards partial fulfillment of requirement for the award of M.D. Degree (Branch -V) in Anatomy. Place: THANJAVUR Date: Dr. K.ARUNA GUIDE CERTIFICATE GUIDE: Prof. Dr.T.Sivakami.M.S., THE PROFESSOR AND HEAD OF THE DEPARTMENT, Department of anatomy, Thanjavur medical college & Hospital, Thanjavur. Remark of the Guide: The work done by DR.K.ARUNA on “A STUDY OF HISTOLOGY OF MAMMARYGLAND – VARIOUS AGES’’ is under my supervision and I assure that this candidate will abide by the rules of the Ethical Committee. GUIDE:Prof.Dr .T.SIVAKAMI., THE PROFESSOR AND HOD, Department of Anatomy, Thanjavur medical college & Hospital, Thanjavur ACKNOWLEDGEMENT Iam extremely Thankful to my teacher Dr.T.Sivakami M.S., Professor & Head ,Vice principal, Thanjavur medical college, Thanjavur.
    [Show full text]
  • The Effect of L-Arginine and Antagonist L-Name in the Mammary Gland Of
    JPCS Vol(6) ● Jan-March 2013 www.arpapress.com/Volumes/JPCS/Vol6/JPCS_6_04.pdf THE EFFECT OF L-ARGININE AND ANTAGONIST L-NAME ON THE MAMMARY GLAND OF PREGNANT MICE Marwa Abdul Alkareem, Mohanad A. AlBayati1& WaelKhamas2 1University of Baghdad: College of Veterinary Medicine Department of Physiology and Pharmacology, Iraq 2Western University of Health Sciences: College of Veterinary Medicine, CA. Pomona, USA. ABSTRACT L-arginine is well known as a precursor of Nitric Oxide (NO). NO is one of a major endothelial-derived relaxing factor listed as an endogenous messenger molecule involved in a variety of dependent physiological events through increasing blood flow then blood volume in tissues. L-arginine promotes various fertility parameters and improves fetal traits by acceleration of dramatic molecular events. All of that resultsin a speculation to have superior pups weight through exaggerated mammary gland function and improve milk quality. This study was performed to pharmacologically enhance the performance of the mammary gland by using L-arginine as a forerunner of NO. The study protocol consisted of a total number of 130 pregnant and lactating mice separated into two main groups equally; each one was randomly divided into 3 subgroups [control, L-arginine and L-NAME (served as NO inhibitor)]. L-arginine dosed orally with the following groups: 100, 150, 200, 250 and 300 mg/kg BW daily in pregnant and lactating mice, L-NAME dose 100 mg/kg BW daily dose IP and normal saline was given to 20 female mice which served as control (10 pregnantand 10 lactating respectively).Four mammary glands were evaluated and then yielded the following:Histological and stereological profiles, Development and branching of the mammary alveoli and the reduction of adipose tissue with profuse milk accumulation were observed.
    [Show full text]
  • University of Cincinnati
    UNIVERSITY OF CINCINNATI Date:_9/4/07______________ I, _Yuxin Feng________________________________________________, hereby submit this work as part of the requirements for the degree of: Doctor of Philosophy in: Cell and Cancer Biology It is entitled: Mechanism of estrogen receptor alpha action and the consequence of its conditional deletion on Mammary gland development and function This work and its defense approved by: Chair: Sohaib Khan, Ph.D.____________ Karen E.Knudsen, Ph.D.________ Elwood V. Jensen, Ph.D._______ Susan Waltz, Ph.D.____________ Nelson Horseman, Ph.D.________ Robert Brackenbury, Ph.D._____ Mechanism of estrogen receptor-alpha action and the consequence of its conditional deletion on mammary gland development and function A dissertation submitted to the Division of Research and Advanced Studies of the University of Cincinnati in partial fulfillment of the requirements for the degree of DOCTORATE OF PHILOSOPHY (Ph.D.) in the Department of Cell and Cancer Biology of the College of Medicine 2007 by Yuxin Feng M. S., Nankai University, 1997 B. S., Ocean University of Qingdao, 1990 Committee Chair: Sohaib Khan, Ph.D. ABSTRACT ERα is a critical regulator in breast cancer and mammary gland development. Deregulation of ER signaling correlates with abnormal mammary gland development and breast cancer. However, the role of epithelial ER remains to be clarified in vivo and the mechanism of ER signaling regulation is far from comprehensive. We hypothesize that 1) mammary epithelial ER plays critical roles in mammary gland development during pregnancy and lactation and that 2) novel, as yet identified factors in ER transcriptional regulation are involved in breast cancer development.
    [Show full text]
  • Part I Integrins: the Basic Machinery for Cell Adhesion 1.1 Cell Adhesion Receptors 1.2 Integrins and Cell Adhesion 1.2.1
    β1 integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli Inauguraldissertation zur Erlangung der Würde eines Doktors der Philosophie vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel von Na Li People's Republic of China Leiter der Arbeit : Prof. Dr. Nancy Hynes Friedrich Miescher Institute for Biomedical Research Basel, 2005 Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät Auf Antrag von Prof. Dr. Max M Burger, Prof. Dr. Nancy Hynes, PD Dr. Patrick Matthias. Basel, den 05.April, 2005 Prof. Dr. Marcel Tanner Dekan Summary Integrins are cell adhesion receptors which mediate interactions between the extracellular matrix and the actin cytoskeleton. They are heterodimers composed of α and β subunits. As adhesion receptors, integrins are important for cell-cell and cell-matrix interactions and therefore are essential for the structural integrity of an organ. Moreover, integrin-extracellular matrix interactions play important roles in the coordinated integration of external and internal cues that are essential for proper development. β1 integrin is the most widely expressed integrin and controls various developmental processes, including neurogenesis, chondrogenesis, skin and hair follicle morphogenesis, and myoblast fusion. To determine the role of β1 integrin in normal development of the mouse mammary gland, with a particular emphasis on how β1 integrins influcence proliferation, differentiation and apoptosis; we examined the consequence of conditional deletion of β1 integrin in mammary epithelia. Itgβ1flox/flox mice were crossed with WAPiCre transgenic mice, which led to specific ablation of β1 integrin in luminal alveolar epithelial cells. In the β1 integrin mutant mammary gland, individual alveoli were disorganized resulting from alterations in cell-basement membrane associations.
    [Show full text]
  • Epithelial–Stromal Interactions in the Mouse and Human Mammary Gland in Vivo
    Endocrine-Related Cancer (2004) 11 437–458 REVIEW Epithelial–stromal interactions in the mouse and human mammary gland in vivo Hema Parmar and Gerald R Cunha University of California, 3rd and Parnassus, Department of Anatomy, HSW 1323, San Francisco, CA 94143, USA (Requests for offprints should be addressed to G R Cunha; Email: [email protected]) Abstract This review deals with the development and hormonal responses of mouse and human mammary glands. A major focus of the review is the role of mesenchymal–epithelial interactions in embryonic mammary development and the role of stromal–epithelial interactions in mammary gland biology. Finally, we present a new model for studying growth, differentiation and hormonal response in human breast epithelium grown in vivo in nude mouse hosts. This new model involves the construction of tissue recombinants composed of human or mouse mammary fibroblasts plus human breast epithelium in polymerized collagen gels. In the model, mouse mammary fibroblasts and human breast fibroblasts appear to support the normal differentiation and growth of human breast epithelium equally. This observation raises the possibility of using mouse mammary fibroblasts from various mutant mice to assess the role of specific paracrine-acting gene products in human mammary gland biology and carcinogenesis. Endocrine-Related Cancer (2004) 11 437–458 Introduction mammary duct invades the mammary fat pad at E17 and subsequently forms a small branched ductal tree. At the The mammary gland is a useful model in which to study time of birth, 15–20 branching ducts are present within epithelial–stromal interactions, as these interactions are the developing murine fat pad.
    [Show full text]
  • Relationship Between Histology, Development and Tumorigenesis of Mammary Gland in Female Rat
    Exp. Anim. 65(1), 1–9, 2016 —Review— Relationship between histology, development and tumorigenesis of mammary gland in female rat Ján LÍŠKA1), Július BRTKO2), Michal DUBOVICKÝ3), Dana MACEJOVÁ2), Viktória KISSOVÁ4), Štefan POLÁK1), and Eduard UJHÁZY3) 1) Institute of Histology and Embryology, Medical Faculty of Comenius University, Sasinkova 4, Bratislava 811 08, Slovak Republic 2) Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlárska 3, Bratislava 833 06, Slovak Republic 3) Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Dúbravská cesta 9, Bratislava 841 04, Slovak Republic 4) Department of Pathological Anatomy, University of Veterinary Medicine and Pharmacy, Komenského 73, Košice 041 81, Slovak Republic Abstract: The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer. An early first full-term pregnancy may have a protective effect. Rodent models are useful for investigating potential breast carcinogens. The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential.
    [Show full text]
  • Mammary Gland Development Hector Macias and Lindsay Hinck∗
    Advanced Review Mammary gland development Hector Macias and Lindsay Hinck∗ The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes. Regulated by epithelial–mesenchymal interactions, the placodes descend into the underlying mesenchyme and produce the rudimentary ductal structure of the gland present at birth. Subsequent stages of development—pubertal growth, pregnancy, lactation, and involution—occur postnatally under the regulation of hormones. Puberty initiates branching morphogenesis, which requires growth hormone (GH) and estrogen, as well as insulin-like growth factor 1 (IGF1), to create a ductal tree that fills the fat pad. Upon pregnancy, the combined actions of progesterone and prolactin generate alveoli, which secrete milk during lactation. Lack of demand for milk at weaning initiates the process of involution whereby the gland is remodeled back to its prepregnancy state. These processes require numerous signaling pathways that have distinct regulatory functions at different stages of gland development. Signaling pathways also regulate a specialized subpopulation of mammary stem cells that fuel the dramatic changes in the gland occurring with each pregnancy. Our knowledge of mammary gland development and mammary stem cell biology has significantly contributed to our understanding of breast cancer and has advanced the discovery of therapies to treat this disease. © 2012 Wiley Periodicals, Inc. How to cite this article: WIREs Dev Biol 2012. doi: 10.1002/wdev.35 INTRODUCTION and luminal. The basal epithelium consists of myoep- ithelial cells, which generate the outer layer of the he mammary gland (breast) distinguishes mam- gland, and a small population of stem cells, which mals from all other animals with its unique T supply the different cell types.
    [Show full text]
  • Notch Signaling Is Important in the Survival, Proliferation, and Self-Renewal of the Putative Breast Cancer Stem Cell Population
    Loyola University Chicago Loyola eCommons Dissertations Theses and Dissertations 2010 Notch Signaling Is Important in the Survival, Proliferation, and Self-Renewal of the Putative Breast Cancer Stem Cell Population Peter Grudzien Loyola University Chicago Follow this and additional works at: https://ecommons.luc.edu/luc_diss Part of the Cell and Developmental Biology Commons Recommended Citation Grudzien, Peter, "Notch Signaling Is Important in the Survival, Proliferation, and Self-Renewal of the Putative Breast Cancer Stem Cell Population" (2010). Dissertations. 87. https://ecommons.luc.edu/luc_diss/87 This Dissertation is brought to you for free and open access by the Theses and Dissertations at Loyola eCommons. It has been accepted for inclusion in Dissertations by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. Copyright © 2010 Peter Grudzien LOYOLA UNIVERSITY CHICAGO NOTCH SIGNALING IS IMPORTANT IN THE SURVIVAL, PROLIFERATION, AND SELF-RENEWAL OF THE PUTATIVE BREAST CANCER STEM CELL POPULATION A DISSERTATION SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL IN CANDIDACY FOR THE DEGREE OF DOCTOR OF PHILOSOPHY PROGRAM IN MOLECULAR AND CELLULAR BIOCHEMISTRY BY PETER GRUDZIEN CHICAGO, IL DECEMBER 2010 Copyright by Peter Grudzien, 2010 All rights reserved. ACKNOWLEDGEMENTS I would first like to express my gratitude to my mentor, Dr. Kimberly Foreman, who is a wonderful teacher and has guided me throughout my entire project. Kim has a wonderful approach to teaching science by first demonstrating various techniques and then allowing me to learn them at my own pace.
    [Show full text]
  • Mammary Gland Development Methods and Protocols M ETHODS in MOLECULAR BIOLOGY
    Methods in Molecular Biology 1501 Finian Martin Torsten Stein Jillian Howlin Editors Mammary Gland Development Methods and Protocols M ETHODS IN MOLECULAR BIOLOGY Series Editor John M. Walker School of Life and Medical Sciences University of Hertfordshire Hatfield, Hertfordshire, AL10 9AB , UK For further volumes: http://www.springer.com/series/7651 Mammary Gland Development Methods and Protocols Edited by Finian Martin School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland Torsten Stein Institute of Cancer Sciences, College of MVLS, University of Glasgow, Glasgow, UK Jillian Howlin Division of Oncology-Pathology, Lund University Cancer Center/Medicon Village, Lund, Sweden Editors Finian Martin Torsten Stein School of Biomolecular and Biomedical Science Institute of Cancer Sciences University College Dublin College of MVLS Belfield , Dublin , Ireland University of Glasgow Glasgow , UK Jillian Howlin Division of Oncology-Pathology Lund University Cancer Center/Medicon Village Lund , Sweden ISSN 1064-3745 ISSN 1940-6029 (electronic) Methods in Molecular Biology ISBN 978-1-4939-6473-4 ISBN 978-1-4939-6475-8 (eBook) DOI 10.1007/978-1-4939-6475-8 Library of Congress Control Number: 2016945163 © Springer Science+Business Media New York 2017 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc.
    [Show full text]