Epithelial cell types and their evolution in the rat mammary gland determined by immunological markers.

Dulbecco, Renato; Unger, Michael; Armstrong, B; Bowman, M; Syka, Peter

doi:10.1073/pnas.80.4.1033

Cited by 62 publications

(27 citation statements)

References 8 publications

(4 reference statements)

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“…The gland consists of at least four recognizable cell types: adipocytes, fibroblasts, myoepithelial, and epithelial. Regional specialization of epithelial types might also distinguish basal from ductal and secretory epithelium (7)(8)(9)(10) differential tissue-specific response of embryonic mammary epithelium to embryonic mesenchyme in homeotypic and heterotypic recombinant organ cultures. When mammary epithelium is combined with mammary mesenchyme, the result is typical monopoidal branching patterns indicative of normal mammary morphogenesis.…”

Section: Mammary Gland Histogenesismentioning

confidence: 99%

Regulation of Functional Cytodifferentiation and Histogenesis in Mammary Epithelial Cells: Role of the Extracellular Matrix

Bissell¹,

Ram²

1989

Environmental Health Perspectives

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Primary mammary epithelial cells provide a versatile system for the study of hormone and extracellular matrix (ECM) influences on tissue-specific gene expression. We have characterized the formation of aveolarlike morphogenesis and mammary-specific functional differentiation that occur when these cells are cultured on a reconstituted basement membrane (EHS). Cells cultured on EHS exhibit many ultrastructural and biochemical features indicative of polarized and functionally differentiated mammary epithelium in vivo. The increased expression and specific vectorial secretion of milk proteins into lumina formed in culture are accompanied by large increases in milk protein mRNA expression. However, when individual ECM components are tested, smaller increases in milk protein mRNA are measured on heparan sulfate proteoglycan (HSPG) and laminin, and these responses are not associated with full functional cytodifferentiation or histotypic configuration. This indicates that multiple levels of regulation are involved in mammary-specific gene expression, and that in addition to individual ligand requirements cooperative interactions between various ECM molecules and cells are necessary for functional differentiation in culture. We have also shown that endogenous production of ECM molecules and changes in cell geometry are correlated with changes in functional and histogenic gene expression. We have previously proposed a model of cell-ECM interactions that is consistent with these data.

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Section: Mammary Gland Histogenesismentioning

confidence: 99%

Regulation of Functional Cytodifferentiation and Histogenesis in Mammary Epithelial Cells: Role of the Extracellular Matrix

Bissell¹,

Ram²

1989

Environmental Health Perspectives

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“…This approach has been used in our laboratory for studying the pathways of cell differentiation in the mammary gland (1). Antibodies to cytokeratins are especially useful in this context because there are many different kinds of cytokeratins, which display considerable cell specificity.…”

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confidence: 99%

“…For instance, Lane (15) has shown that monoclonal antibodies to cytokeratins from PtK1 cells recognize cells in the rat mammary gland. We have found that one of these antibodies (Le6l) is highly selective for certain cell types (1). By taking advantage of this crossreactivity, we have prepared a set of monoclonal antibodies from mice immunized with total cow muzzle keratin.…”

mentioning

confidence: 99%

Developmental regulation of cytokeratins in cells of the rat mammary gland studied with monoclonal antibodies.

Allen¹,

Dulbecco²,

Syka³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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We have isolated two monoclonal antibodies to cytokeratins and determined their cell specificities. They display interesting localization within the rat mammary gland. One (lA10) shows specificity for myoepithelial cells; the other (24B42) is specific for lumenal cells at various stages of development. These two monoclonal antibodies and three others to cytokeratin previously isolated were used in conjunction with antibodies to myosin and collagen IV to confirm and extend our previous findings on epithelial cell types and development within the mammary gland.Antibodies, especially monoclonal antibodies, are very useful for identifying cell types using immunocytological methods. This approach has been used in our laboratory for studying the pathways of cell differentiation in the mammary gland (1). Antibodies to cytokeratins are especially useful in this context because there are many different kinds of cytokeratins, which display considerable cell specificity.The cytokeratins are expressed by a multigene family that is developmentally regulated (see refs. 2 and 3 for reviews). They are expressed mostly in epithelia but also in mesothelial cells (4). Every tissue has a complex pattern of these peptides, which can be distinguished by their isoelectric point and electrophoretic mobility in gels. Many tissues share the same peptides (5, 6). The distribution of the peptides, ascertained by either extraction or by immunohistochemical methods using polyclonal antisera, differs in different organs or in different parts of the same organ-for instance in different layers of the epidermis. Similar peptides are found in different mammalian species. Using monoclonal antibodies (7), the existence of both peptide-specific and common epitopes was observed (8). Monoclonal antibodies with considerable specificity (8-10), as well as some with broad crossreactivity (11), were identified by immunohistochemistry. Using polyclonal antisera to partially purified peptides it was shown by immunohistochemistry that cytokeratins are not uniformly distributed in the mammary gland (11-13). Quantitative differences were observed between myoepithelial and epithelial cells, and in the latter cells, between ductal and secretory alveolar cells (12)(13)(14).Cytokeratins show considerable crossreactivity among species. For instance, Lane (15) has shown that monoclonal antibodies to cytokeratins from PtK1 cells recognize cells in the rat mammary gland. We have found that one of these antibodies (Le6l) is highly selective for certain cell types (1). By taking advantage of this crossreactivity, we have prepared a set of monoclonal antibodies from mice immunized with total cow muzzle keratin. We report here on the properties of two antibodies that have considerable cell specificities. These antibodies are very useful for studying the cell types present in the rat mammary gland. They allow a further refinement of the pathway of cell differentiation in this organ. We also compare these monoclonal antibodies with three others from mice immunized w...

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“…Later, moderate ductal growth occurs until puberty, when a more pronounced development of the ducts leads to the formation of a ductal tree (2). In cycling virgin mice, the parenchyma consists of a highly organized system of ducts with terminal end-buds that represent the major sites of ductal growth (3)(4)(5) and give rise to alveolar buds (6). Alveolar buds in turn generate alveoli that eventually may secrete milk proteins during pregnancy and lactation (7).…”

mentioning

confidence: 99%

Dome formation in cell cultures as expression of an early stage of lactogenic differentiation of the mammary gland

Zucchi

Bini

Albani

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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The study of the development of the mammary gland at the molecular level in the animal is difficult because of the complex tissue organization of the gland. We have previously developed an in vitro system for genetic analysis of mammary cell differentiation, based on the cell line LA7 clonally derived from a rat mammary adenocarcinoma. This cell line, after induction with DMSO, differentiates forming structures called domes. This process is under strict gene regulation, and we have previously identified several of the genes involved. In the present paper, we have defined the meaning of dome formation in relation to mammary development, by showing that treatment of LA7 cells with the lactogenic hormones hydrocortisone and prolactin induces dome formation; in the animal, these hormones precede and accompany milk production. Moreover, dome formation is accompanied by expression within the cells of the milk protein genes WDMN1 and ␤-casein, which are differentiation markers for the gland during pregnancy and lactation. We also show that two proteins, highly expressed in the mammary gland during lactation, HSP90-␤ and annexin I, are strongly expressed in DMSO-induced LA7 cells. Both proteins are essential in the formation of domes because when their synthesis is blocked by antisense RNA oligonucleotides, dome formation is abolished. Thus our in vitro system is a model for lobulo-alveolar development, and the genes identified in the pathway of dome formation are likely to be involved in the early differentiation steps occurring in the rat mammary gland during pregnancy and lactation.

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Epithelial cell types and their evolution in the rat mammary gland determined by immunological markers.

Cited by 62 publications

References 8 publications

Regulation of Functional Cytodifferentiation and Histogenesis in Mammary Epithelial Cells: Role of the Extracellular Matrix

Regulation of Functional Cytodifferentiation and Histogenesis in Mammary Epithelial Cells: Role of the Extracellular Matrix

Developmental regulation of cytokeratins in cells of the rat mammary gland studied with monoclonal antibodies.

Dome formation in cell cultures as expression of an early stage of lactogenic differentiation of the mammary gland

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