Distinct stem cells contribute to mammary gland development and maintenance

Keymeulen, Alexandra Van; Rocha, Ana Sofia; Ousset, Marielle; Beck, Benjamin; Bouvencourt, Gaëlle; Rock, Jason R.; Sharma, Neha; Dekoninck, Sophie; Blanpain, Cédric

doi:10.1038/nature10573

Cited by 772 publications

(972 citation statements)

References 36 publications

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“…In postnatal unperturbed mammary glands, both luminal and myoepithelial lineages contain long-lived uni-potent stem cells that display extensive renewing capacities, as demonstrated by their ability to clonally expand during morphogenesis and adult life as well as undergo massive expansion during several cycles of pregnancy [116]. The demonstration that the mammary gland contains different types of long-lived stem cells has profound implications for our understanding of mammary gland physiology and will be instrumental in unraveling the cells at the origin of breast cancers [116]. The invasive and proliferative processes of mammogenesis in the fetal mammary stem cell state resemble phases of cancer progression [117].…”

Section: Estrogen Signaling In Breast Cancer Stem Cellsmentioning

confidence: 99%

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

Zhou

Qiao

Shetty

et al. 2013

Cell. Mol. Life Sci.

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Estrogen and estrogen receptors (ERs) are critical regulators of breast epithelial cell proliferation, differentiation, and apoptosis. Compromised signaling vis-à-vis the estrogen receptor is believed © Springer Basel 2013 yow4@pitt.edu. ), which predicts for response to endocrine-based therapy; however, innate or acquired resistance to endocrinebased drugs remains a serious challenge. The complexity of regulation for estrogen signaling coupled with the crosstalk of other oncogenic signaling pathways is a reason for endocrine therapy resistance. Alternative strategies that target novel molecular mechanisms are necessary to overcome this current and urgent gap in therapy. A thorough analysis of estrogen-signaling regulation is critical. In this review article, we will summarize current insights into the regulation of estrogen signaling as related to breast carcinogenesis and breast cancer therapy. NIH Public Access

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Section: Estrogen Signaling In Breast Cancer Stem Cellsmentioning

confidence: 99%

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

Zhou

Qiao

Shetty

et al. 2013

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

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“…Recent studies of the developing mouse mammary gland have revealed that co-expression of CK14 and CK18 occurs in mammary stem cells during embryogenesis, but not subsequently in the adult gland (30,31); such cells can be detected, however, in mouse mammary tumors (32). In the adult human breast, progenitor and stem cell-enriched subpopulations appear to contain cells that express bi-lineage cytokeratins (7,33).…”

Section: Bi-lineage Cells Possess Increased Colony Formation Capacitymentioning

confidence: 99%

EZH2 promotes a bi-lineage identity in basal-like breast cancer cells

et al. 2012

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The mechanisms regulating breast cancer differentiation state are poorly understood. Of particular interest are molecular regulators controlling the highly aggressive and poorly differentiated traits of basal-like breast carcinomas. Here we show that the Polycomb factor EZH2 maintains the differentiation state of basal-like breast cancer cells, and promotes the expression of progenitorassociated and basal-lineage genes. Specifically, EZH2 regulates the composition of basal-like breast cancer cell populations by promoting a "bi-lineage" differentiation state, in which cells co-express basal-and luminal-lineage markers. We show that human basal-like breast cancers contain a subpopulation of bi-lineage cells, and that EZH2-deficient cells give rise to tumors with a decreased proportion of such cells. Bi-lineage cells express genes that are active in normal luminal progenitors, and possess increased colony formation capacity, consistent with a primitive differentiation state. We found that GATA3, a driver of luminal differentiation, performs a function opposite to EZH2, acting to suppress bi-lineage identity and luminal-progenitor gene expression. GATA3 levels increase upon EZH2 silencing, mediating a decrease in bi-lineage cell numbers. Our findings reveal a novel role for EZH2 in controlling basal-like breast cancer differentiation state and intra-tumoral cell composition.

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“…Both glands contain K5/K14/p63-positive progenitor cells, which give rise to glandular cells with subsequent downregulation of basal keratins/p63 and upregulation of glandular keratins K7/K8/18. Furthermore, it has been demonstrated for breast tissue that the myoepithelial cells originate (embryologically, in transplantation studies, and during physiological regeneration) from K5 and/or K14-positive progenitors 52,53,55 that co-express p63. 16 Our isTILT data provide support for similar cellular differentiation processes in the salivary gland (Boecker et al, manuscript in preparation).…”

Section: Discussionmentioning

confidence: 99%

K5/K14-positive cells contribute to salivary gland-like breast tumors with myoepithelial differentiation

et al. 2013

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Salivary gland-like tumors of the breast show a great variety of architectural patterns and cellular differentiations such as glandular, myoepithelial, squamous, and even mesenchymal phenotypes. However, currently little is known about the evolution and cellular differentiation of these tumors. For that reason, we performed an in situ triple immunofluorescence lineage/differentiation tracing (isTILT) and qRT-PCR study of basal (K5/K14), glandular (K7/K8/18), and epidermal-specific squamous (K10) keratins, p63, and smooth muscle actin (SMA; myoepithelial marker) with the aim to construct and trace different cell lineages and define their cellular hierarchy in tumors with myoepithelial differentiation. isTILT analysis of a series of 28 breast, salivary, and lacrimal gland tumors, including pleomorphic adenomas (n ¼ 8), epithelial-myoepithelial tumors (n ¼ 9), and adenoid cystic carcinomas (n ¼ 11) revealed that all tumor types contained K5/K14-positive progenitor cells in varying frequencies from a few percent up to 15%. These K5/K14-positive tumor cells were found to differentiate to glandular-(K8/18-positive) and myoepithelial-lineage (SMA-positive)-specific cells and were also shown to generate various heterologeous cell differentiations such as squamous and mesenchymal progenies. p63 was co-expressed with K5/K14 in basal-like progenitor cells, myoepithelial, and squamous cells but not in glandular cells. Our results show that the corresponding counterpart tumors of breast and salivary/lacrimal glands have identical cellular compositions. Taken together, our isTILT and RNA-expression data indicate that look-alike tumors of the breast represent a special subgroup of basal-type tumors with benign or usually low malignant potential.

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Distinct stem cells contribute to mammary gland development and maintenance

Cited by 772 publications

References 36 publications

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

EZH2 promotes a bi-lineage identity in basal-like breast cancer cells

K5/K14-positive cells contribute to salivary gland-like breast tumors with myoepithelial differentiation

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