We are analyzing https://link.springer.com/article/10.1186/bcr920.

Title:
Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells | Breast Cancer Research
Description:
Introduction Notch signaling has been implicated in the regulation of cell-fate decisions such as self-renewal of adult stem cells and differentiation of progenitor cells along a particular lineage. Moreover, depending on the cellular and developmental context, the Notch pathway acts as a regulator of cell survival and cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors. Methods In order to determine the role of Notch signaling in mammary cell-fate determination, we have utilized a newly described in vitro system in which mammary stem/progenitor cells can be cultured in suspension as nonadherent
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Keywords {🔍}

cells, notch, mammary, signaling, stem, cell, pubmed, article, dsl, google, scholar, cas, selfrenewal, progenitor, mammospheres, effect, fig, peptide, antibody, treatment, epithelial, mammosphere, myoepithelial, development, culture, differentiation, human, number, formation, activation, cancer, proliferation, expression, normal, suspension, usa, role, lineage, shown, breast, gland, cultures, collagen, vitro, primary, previously, secondary, branching, increase, matrigel,

Topics {✒️}

z-leu-leu-nle-cho recombinant ligand–receptor complexes real-time rt-pcr showed mammary cell-fate determination stem cell biology biases cell-fate decisions hes-1-driven luciferase expression anti-epithelial-specific antigen fire-polished pasteur pipette asymmetric cell-fate decisions mammary stem/progenitor cells blast search analysis human ras-transformed cells retain long-term plasticity dsl-induced luciferase expression notch signalling anti-human fc antibody mammosphere-initiating cells reflects mammosphere-derived cells passaged mouse mammary tumors nomarski contrast-phase image cell-fate decisions cell-fate determination epithelial cell fate mammosphere-derived cells cultivated tertiary mammosphere-derived cells hepatocyte growth factor affect lineage-specific commitment epithelial-specific antigen notch1-expressing cells reveals pgl3-promoter vector neural stem cell human mammary gland mammosphere-derived cells treated mammary stem cell mammary epithelial cells ductal epithelial cells neural stem cells human breast cancer authors’ original file adult mammary gland mammary stem cells luciferase expression induced privacy choices/manage cookies mammary progenitor cells notch4 knockout mouse cell fate control normal stem cell alveolar epithelial cells stem/progenitor cells

Questions {❓}

Brennan K, Brown AMC: Is there a role for Notch signalling in human breast cancer?

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WebPage:
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         headline:Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells
         description:Notch signaling has been implicated in the regulation of cell-fate decisions such as self-renewal of adult stem cells and differentiation of progenitor cells along a particular lineage. Moreover, depending on the cellular and developmental context, the Notch pathway acts as a regulator of cell survival and cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors. In order to determine the role of Notch signaling in mammary cell-fate determination, we have utilized a newly described in vitro system in which mammary stem/progenitor cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists. Utilizing this system, we demonstrate that Notch signaling can act on mammary stem cells to promote self-renewal and on early progenitor cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notch-activating DSL peptide. In addition to acting on stem cells, Notch signaling is also able to act on multipotent progenitor cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial cells. These studies suggest that Notch signaling plays a critical role in normal human mammary development by acting on both stem cells and progenitor cells, affecting self-renewal and lineage-specific differentiation. Based on these findings we propose that abnormal Notch signaling may contribute to mammary carcinogenesis by deregulating the self-renewal of normal mammary stem cells.
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      headline:Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells
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      dateModified:2004-08-16T00:00:00Z
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