The development of epithelial phenotypes in the human fetal and infant breast

Anbazhagan, Ramaswamy; Osin, Pinchas; Bártková, Jiřina; Nathan, B.; Lane, E. Birgitte; Gusterson, Barry A.

doi:10.1002/(sici)1096-9896(199802)184:2<197::aid-path992>3.3.co;2-a

Cited by 16 publications

(29 citation statements)

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“…It appears important to know about the events involved in human breast development, as there is some evidence that breast cancer initiation could occur during the early phases of growth [1]. The fetal period and the first 2 years of life appear to be crucial for some steps in human breast morphogenesis and cytodifferentiation in that epithelial and mesenchymal components undergo morphological [2,3] and functional modifications involving modulation of cytokeratins [4], myoepithelial markers [4], bcl-2 expression [21], growth factors and extracellular matrix proteins [22].…”

Section: Discussionmentioning

confidence: 71%

“…Myoepithelial differentiation was studied by means of an antibody against α-smooth muscle actin (1A4, DBA dilution 1:50), a marker of myoepithelial differentiation in both adult [15] and infant breasts [4].…”

Section: Proteins and Antibodiesmentioning

confidence: 99%

“…Furthermore, an immunohistochemical analysis concerning the distribution of cytoskeletal proteins and other molecules has clarified some aspects of epithelial differentiation and of the relationship between epithelium and stroma during breast development [4,5,22].…”

Section: Introductionmentioning

confidence: 99%

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Bio-morphological events in the development of the human female mammary gland from fetal age to puberty

et al. 2000

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Bio-morphological understanding of the developing human mammary glands may clarify some aspects of breast pathology, including cancer. In particular, some epidemiological data suggests that during fetal growth an altered intrauterine hormonal status, especially a change in estrogen status, could predispose to carcinogenesis. In an attempt to achieve new information on early breast growth, a series of developing human breasts have been analyzed, namely: 4 fetal breasts (28-32 weeks of gestational age), 7 infant breasts (7 h to 2 years) and 1 puberal breast (12 years). In addition to the morphological features, we studied the immunohistochemical expression of some markers involved in morphogenesis, such as MIB-1 for cell proliferation, bcl-2 for apoptosis control, CD34 for vasculogenesis, estrogen (ER) and progesterone (PR) receptors for hormonal profile, and smooth-muscle actin for myoepithelial differentiation. The results were as follows: (a) lobules, absent between 28 weeks and 2 days, were well evident at 2 years of age and at puberty; (b) myoepithelial cells appeared from 28 weeks onward and persisted later with no modification in quantity and distribution; (c) epithelial cell proliferation was constantly low; (d) in all breasts inner epithelial cells showed diffuse bcl-2 positivity, while basal myoepithelial-like cells were generally negative; (e) all breasts were well vascularized with two different patterns: periductal vascularization (PDV) and interductal vascularization (IDV), IDV being always present, whereas PDV was found only in infant breasts; (f) ER and PR were almost absent in fetal and infant breasts, while their expression was high in the epithelial cells of the puberal breast; (g) stromal cells had no hormonal receptors and were heterogeneous for proliferation and bcl-2 expression. Interestingly, two fetal breasts showed high proliferation and high ER expression, respectively, in their epithelial compartment. This could be the expression of an altered hormonal environment in utero, representing a basis for possible subsequent cancer initiation.

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Section: Discussionmentioning

confidence: 71%

Section: Proteins and Antibodiesmentioning

confidence: 99%

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Bio-morphological events in the development of the human female mammary gland from fetal age to puberty

et al. 2000

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“…It is also clear that somewhere within the TEBs there is a stem cell activity [16] most likely located within the cap cells, such that they also give rise the body cells as well as the basal cell layer [10,12,15]. In humans, structures analogous to the TEBs have been observed [17]. Between three and approximately 10 -12 weeks of age, the ducts grow into the mammary fat pad, branching at regular intervals, to create a network of primary and secondary ducts which form continuous channels from the site of milk production during lactation, the secretory alveoli, to the nipple.…”

Section: Mammary Gland Developmentmentioning

confidence: 99%

Common Molecular Mechanisms of Mammary Gland Development and Breast Cancer

Molyneux

Regan

Smalley

2007

Cell. Mol. Life Sci.

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The mammary gland undergoes major developmental changes during puberty and pregnancy. It is thought that stem cells drive mammary gland development during puberty and are responsible for tissue maintenance as well as the major growth and remodelling that occurs with every pregnancy. The use of sophisticated cell separation procedures has facilitated the prospective isolation of mammary epithelial stem and differentiated cell subpopulations from the mouse mammary gland, while studies of primary human breast cancers have described sub-populations of tumourigenic cells capable of initiating tumour growth in immuno-compromised mice. These potential tumour 'stem cells' constitute an important therapeutic target population with respect to cancer therapy, as these are likely to be the cells which maintain tumour growth. Understanding the origin of these cells, their relationship to breast cancer subtypes, and how and why they differ from normal breast stem cells will lead to a revolution in tumour understanding, treatment and prevention. (Part of a Multi-author Review).

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“…Recent evidence indicates that CK19 is expressed by diverse stem cell compartments. Thus, CK19 is one of the earliest keratins expressed in the human embryo [103], and whereas the fetal breast contains homogenous expression of CK19, CK19-negative luminal epithelial cells arise in adulthood [104]. Studies of other organs, including liver, pancreas, skin, testes and prostate, have shown that the stem cell compartments express CK19 [105][106][107][108][109][110].…”

Section: E6-and E7-immortalized Cell Lines As a Model For Breast Morpmentioning

confidence: 99%

Immortalization protocols used in cell culture models of human breast morphogenesis

Gudjonsson

Villadsen²,

Rønnov‐Jessen³

et al. 2004

CMLS, Cell. Mol. Life Sci.

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Defining the key players in normal breast differentiation is instrumental to understanding how morphogenesis becomes defective during breast cancer progression. During the past 2 decades much effort has been devoted to the development of technologies for purification and expansion of primary human breast cells in culture and optimizing a relevant microenvironment, which may help to define the niche that regulates breast differentiation and morphogenesis. In contrast to the general property of cancer, normal human cells have a finite lifespan. After a defined number of population doublings, normal cells enter an irreversible proliferation-arrested state referred to as replicative senescence. To overcome this obstacle for continuous long-term studies, replicative senescence can be bypassed by treatment of cells with chemical agents such as benzopyrene, by radiation or by transfection with viral oncogenes or the gene for human telomerase (human telomerase reverse transcriptase, hTERT). A drawback of some of these protocols is a concurrent introduction of chromosomal changes, which sometimes leads to a transformed phenotype and selection of a subpopulation, which may not be representative of the tissue of origin. In recent years, we have sought to establish immortalized primary breast cells, which retain crucial characteristics of their original in situ tissue pattern. This review discusses various approaches to immortalization of breast-derived epithelial and stromal cells and the application of such cell lines for studies on human breast morphogenesis.

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The development of epithelial phenotypes in the human fetal and infant breast

Cited by 16 publications

References 0 publications

Bio-morphological events in the development of the human female mammary gland from fetal age to puberty

Bio-morphological events in the development of the human female mammary gland from fetal age to puberty

Common Molecular Mechanisms of Mammary Gland Development and Breast Cancer

Immortalization protocols used in cell culture models of human breast morphogenesis

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