Abstract:
INTRODUCTION:Studies have identified multi-potent stem cells in the adult mammary gland. More recent studies have suggested that the embryonic mammary gland may also contain stem/progenitor cells that contribute to initial ductal development. We were interested in determining whether embryonic cells might also directly contribute to long-lived stem cells that support homeostasis and development in the adult mammary gland. METHODS:We used DNA-label retention to detect long label-retaining cells in the mammary gland. Mouse embryos were labeled with 5-ethynl-2'-deoxyuridine (EdU) between embryonic day 14.5 and embryonic day 18.5 and were subsequently sacrificed and examined for EdU retention at various intervals after birth. EdU retaining cells were co-stained for various lineage markers and identified after fluorescence activated cell sorting analysis of specific epithelial subsets. EdU-labeled mice were subjected to subsequent 5-bromo-2'-deoxyuridine administration to determine whether EdU-labeled cells could re-enter the cell cycle. Finally, EdU-labeled cells were grown under non-adherent conditions to assess their ability to form mammospheres. RESULTS:We demonstrate embryonically-derived, long label-retaining cells (eLLRCs) in the adult mammary gland. eLLRCs stain for basal markers and are enriched within the mammary stem cell population identified by cell sorting. eLLRCs are restricted to the primary ducts near the nipple region. Interestingly, long label retaining cells (labeled during puberty) are found just in front of the eLLRCs, near where the ends of the ducts had been at the time of DNA labeling in early puberty. A subset of eLLRCs becomes mitotically active during periods of mammary growth and in response to ovarian hormones. Finally, we show that eLLRCs are contained within primary and secondary mammospheres. CONCLUSIONS:Our findings suggest that a subset of proliferating embryonic cells subsequently becomes quiescent and contributes to the pool of long-lived mammary stem cells in the adult. eLLRCs can re-enter the cell cycle, produce both mammary lineages and self-renew. Thus, our studies have identified a putative stem/progenitor cell population of embryonic origin. Further study of these cells will contribute to an understanding of how quiescent stem cells are generated during development and how fetal exposures may alter future breast cancer risk in adults.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Boras-Granic K,Dann P,Wysolmerski JJdoi
10.1186/s13058-014-0487-6subject
Has Abstractpub_date
2014-12-03 00:00:00pages
487issue
6eissn
1465-5411issn
1465-542Xpii
s13058-014-0487-6journal_volume
16pub_type
杂志文章abstract:INTRODUCTION:Mammographic density has been established as a strong risk factor for breast cancer, primarily using digitized film mammograms. Full-field digital mammography (FFDM) is replacing film mammography, has different properties than film, and provides both raw and processed clinical display representation images...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3372
更新日期:2013-01-04 00:00:00
abstract:BACKGROUND:Fragments of collagen type I containing the epitope AHDGGR (CTX) are generated during bone resorption. The aspartyl-glycine (DG) site within CTX is synthesised in the L-aspartyl peptide (alphaL) form, but converts to the age-modified forms L-isoaspartyl peptide (betaL) and D-aspartyl peptide (alphaD) over ti...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr607
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:Increased mammographic breast density is one of the strongest risk factors for breast cancer. While two-thirds of the variation in mammographic density appears to be genetically influenced, few variants have been identified. We examined the association of inherited variation in genes from pathways that med...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3088
更新日期:2012-01-07 00:00:00
abstract:INTRODUCTION:The aim of this study was to develop and validate a prognostication model to predict overall and breast cancer specific survival for women treated for early breast cancer in the UK. METHODS:Using the Eastern Cancer Registration and Information Centre (ECRIC) dataset, information was collated for 5,694 wom...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2464
更新日期:2010-01-01 00:00:00
abstract::c-Met is a receptor tyrosine kinase that upon binding of its ligand, hepatocyte growth factor (HGF), activates downstream pathways with diverse cellular functions that are important in organ development and cancer progression. Anomalous c-Met signalling has been described in a variety of cancer types, and the receptor...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/s13058-015-0547-6
更新日期:2015-04-08 00:00:00
abstract:INTRODUCTION:BRCA1 and BRCA2 mutation carriers are at increased risk for developing both breast and ovarian cancer. It has been suggested that carriers of BRCA1/2 mutations may also be at increased risk of having recurrent (three or more) miscarriages. Several reproductive factors have been shown to influence the risk ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究
doi:10.1186/bcr1387
更新日期:2006-01-01 00:00:00
abstract::PIK3CA mutations confer constitutive activation of PI3K, which initiates intracellular kinase signaling cascades that promote cell proliferation and survival. Recent studies by Meyer and colleagues, and Liu and colleagues demonstrate that expression of the H1047R exon 20 mutant of PIK3CA in luminal mammary epithelial ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3103
更新日期:2012-02-07 00:00:00
abstract:INTRODUCTION:Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondria...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0567-2
更新日期:2015-04-25 00:00:00
abstract:INTRODUCTION:Epithelial-to-mesenchymal transition (EMT) promotes cell migration and is important in metastasis. Cellular proliferation is often downregulated during EMT, and the reverse transition (MET) in metastases appears to be required for restoration of proliferation in secondary tumors. We studied the interplay b...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3580
更新日期:2013-11-27 00:00:00
abstract:BACKGROUND:Breast cancer subtype can be classified using standard clinical markers (estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)), supplemented with additional markers. However, automated biomarker scoring and classification schemes have not been standardized. T...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0939-5
更新日期:2018-02-06 00:00:00
abstract::Despite the progress achieved in breast cancer screening and therapeutic innovations, the basal-like subtype of breast cancer (BLBC) still represents a particular clinical challenge. In order to make an impact on survival in this type of aggressive breast cancer, new targeted therapeutic agents are urgently needed. Ab...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr3401
更新日期:2013-03-28 00:00:00
abstract:BACKGROUND:Recent genome-wide profiling by sequencing and distinctive chromatin signatures has identified thousands of long non-coding RNA (lncRNA) species (>200 nt). LncRNAs have emerged as important regulators of gene expression, involving in both developmental and pathological processes. While altered expression of ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0853-2
更新日期:2017-05-30 00:00:00
abstract:INTRODUCTION:Bcl-2 and Bcl-xL confer resistance to apoptosis, thereby reducing the effectiveness of chemotherapy. We examined the relationship between the expression of Bcl-2 and Bcl-xL and chemosensitivity of breast cancer cells, with the aim of developing specific targeted therapy. METHODS:Four human breast cancer c...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1323
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:The HER (human EGFR related) family of receptor tyrosine kinases (HER1/EGFR (epidermal growth factor receptor)/c-erbB1, HER2/c-erbB2, HER3/c-erbB3 and HER4/c-erbB4) shares a high degree of structural and functional homology. It constitutes a complex network, coupling various extracellular ligands to intrac...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1843
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:Menopausal hormone therapies vary widely in their effects on breast cancer risk, and the mechanisms underlying these differences are unclear. The primary goals of this study were to characterize the mammary gland transcriptional profile of estrogen + progestin therapy in comparison with estrogen-alone or t...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3456
更新日期:2013-01-01 00:00:00
abstract::Anti-angiogenic therapies have demonstrated their value in the setting of advanced cancer, and are being explored for use in micrometastatic disease. Recent preclinical studies suggest that adjuvant anti-vascular endothelial growth factor (VEGF) therapies may increase the risk of metastasis. How concerning are these p...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2250
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:The tumour-suppressive effects of transforming growth factor-beta (TGF-beta) are well documented; however, the mechanistic basis of these effects is not fully understood. Previously, we showed that a non-canonical member of the Wingless-related protein family, Wnt5a, is required for TGF-beta-mediated effec...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2244
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:This study was designed to determine if and how a non-toxic, naturally occurring bioflavonoid, galangin, affects proliferation of human mammary tumor cells. Our previous studies demonstrated that, in other cell types, galangin is a potent inhibitor of the aryl hydrocarbon receptor (AhR), an environmental c...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1391
更新日期:2006-01-01 00:00:00
abstract::The Breast Cancer Site Group (BCSG) of the National Cancer Institute of Canada (NCIC) Clinical Trials Group (CTG) has conducted a wide variety of clinical trials focussing on large phase III trials of adjuvant chemotherapy, adjuvant hormonal therapy, and optimal delivery of adjuvant radiation therapy. The Group has al...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr979
更新日期:2005-01-01 00:00:00
abstract::The transition from pregnancy to lactation is a critical event in the survival of the newborn since all the nutrient requirements of the infant are provided by milk. While milk contains numerous components, including proteins, that aid in maintaining the health of the infant, lactose and milk fat represent the critica...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr1653
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast canc...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0953-7
更新日期:2018-04-16 00:00:00
abstract:INTRODUCTION:Mammary stem cells are bipotential and suggested to be the origin of breast cancer development, but are elusive and vaguely characterized. Breast tumors can be divided into subgroups, each one requiring specific treatment. To determine a possible association between mammary stem cells and breast cancer, a ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2256
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Menopausal hormone therapy (HT) is typically withheld from breast cancer survivors because of concerns about risk for recurrence. Our objectives were to estimate the effects of HT on recurrence in breast cancer survivors and to examine the reliability of these estimates. METHODS:In a systematic review of ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,meta分析
doi:10.1186/bcr1035
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Compromised patterns of gene expression result in genomic instability, altered patterns of gene expression and tumour formation. Specifically, aberrant DNA hypermethylation in gene promoter regions leads to gene silencing, whereas global hypomethylation events can result in chromosomal instability and onco...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr799
更新日期:2004-01-01 00:00:00
abstract::Two articles previously published in Breast Cancer Research illustrate the high rates of breast cancer in Marin County, a wealthy, urban county immediately northwest of the city of San Francisco. I herein comment on these articles, and on the political/psychological/scientific dilemma presented by regions with high ca...
journal_title:Breast cancer research : BCR
pub_type: 评论,杂志文章,评审
doi:10.1186/bcr633
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:Earlier menarche is related to subsequent breast cancer risk, yet international differences in the age and tempo of other pubertal milestones and their relationships with body mass index (BMI) are not firmly established in populations at differing risk for breast cancer. We compared age and tempo of adrena...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-014-0469-8
更新日期:2014-11-15 00:00:00
abstract:BACKGROUND:Mammographic density (MD) is a strong and heritable intermediate phenotype of breast cancer, but much of its genetic variation remains unexplained. METHODS:We conducted a genetic association study of volumetric MD in a Swedish mammography screening cohort (n = 9498) to identify novel MD loci. Associations w...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0954-6
更新日期:2018-04-17 00:00:00
abstract:INTRODUCTION:The invasive, mesenchymal phenotype of CD44posCD24neg breast cancer cells has made them a promising target for eliminating the metastatic capacity of primary tumors. It has been previously demonstrated that CD44neg/lowCD24pos breast cancer cells lack the ability to give rise to their invasive CD44posCD24ne...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2449
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:The Cancer Genome Atlas analysis revealed that somatic EGFR, receptor tyrosine-protein kinase erbB-2 (ERBB2), Erb-B2 receptor tyrosine kinase 3 (ERBB3) and Erb-B2 receptor tyrosine kinase 4 (ERBB4) gene mutations (ERBB family mutations) occur alone or co-occur with somatic mutations in the gene encoding the ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13058-017-0883-9
更新日期:2017-07-27 00:00:00
abstract:INTRODUCTION:It has been suggested that individuals with reduced DNA repair capacities might have increased susceptibility to environmentally induced cancer. In this study, we evaluated if polymorphisms in DNA repair genes XRCC1 (Arg280His, Arg399Gln) and XPD (Lys751Gln) modify individual breast cancer risk, with empha...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1333
更新日期:2005-01-01 00:00:00