Abstract:
INTRODUCTION:During selective segregation of DNA, a cell asymmetrically divides and retains its template DNA. Asymmetric division yields daughter cells whose genome reflects that of the parents', simultaneously protecting the parental cell from genetic errors that may occur during DNA replication. We hypothesized that long-lived epithelial cells are present in immortal, premalignant cell populations, undergo asymmetric division, retain their template DNA strands, and cycle both during allometric growth and during pregnancy. METHODS:The glands of 3-week old immune competent Balb/C female mice were utilized intact or cleared of host epithelium and implanted with ductal-limited, lobule-limited, or alveolar-ductal progenitor cells derived from COMMA-D1 pre-malignant epithelial cells. 5-bromo-2-deoxyuridine (5-BrdU) was administered to identify those cells which retain their template DNA. Nulliparous mice were then either injected with [(3)H]-thymidine ((3)H-TdR) to distinguish 5-BrdU-label retaining cells that enter the cell cycle and euthanized, or mated, injected with (3)H-TdR, and euthanized at various days post-coitus. Sections were stained for estrogen receptor-α(ER-α) or progesterone receptor (PR) via immunohistochemistry. Cells labelled with both 5-BrdU and (3)H-TdR were indicative of label-retaining epithelial cells (LREC). RESULTS:Cells that retained a 5-BrdU label and cells labelled with [(3)H]-thymidine were found in all mice and were typically detected along the branching epithelium of mature mouse mammary glands. Cells containing double-labelled nuclei (LREC) were found in the intact mammary gland of both pregnant and nulliparous mice, and in mammary glands implanted with pre-malignant cells. Double-labelled cells ((3)H-TdR/5-BrdU) represent a small portion of cells in the mammary gland that cycle and retain their template DNA (5-BrdU). Some label-retaining cells were also ER-α or PR positive. LRECs distributed their second label ((3)H-TdR) to daughter cells; and this effect persisted during pregnancy. LRECs, and small focal hyperplasia, were found in all immortalized premalignant mammary implant groups. CONCLUSIONS:The results indicate that a subpopulation of long-lived, label-retaining epithelial cells (LRECs) is present in immortal premalignant cell populations. These LRECs persist during pregnancy, retain their original DNA, and a small percentage express ER-α and PR. We speculate that LRECs in premalignant hyperplasia represent the long-lived (memory) cells that maintain these populations indefinitely.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Bussard KM,Boulanger CA,Kittrell FS,Behbod F,Medina D,Smith GHdoi
10.1186/bcr2754subject
Has Abstractpub_date
2010-01-01 00:00:00pages
R86issue
5eissn
1465-5411issn
1465-542Xpii
bcr2754journal_volume
12pub_type
杂志文章abstract:INTRODUCTION:Global gene expression analysis of tumor samples has been a valuable tool to subgroup tumors and has the potential to be of prognostic and predictive value. However, tumors are heterogeneous, and homogenates will consist of several different cell types. This study was designed to obtain more refined expres...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0530-2
更新日期:2015-02-21 00:00:00
abstract::Adjuvant hormonal therapy for postmenopausal women with early stage breast cancer has become far more complex over the past several years. This commentary reviews the current status of the five major trials evaluating the use of the aromatase inhibitors in the adjuvant setting. The data currently available suggest tha...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr1347
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Classification of breast cancers according to the HER-2 oncogene status is of central importance in the selection of post-surgical therapies. A decrease in the proportion of HER-2-positive breast cancer has been suspected, but no data on the incidence trends at population level have been reported. METHODS...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2322
更新日期:2009-01-01 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::The seventh annual meeting of the European Network of Breast Development and Cancer Laboratories, held in Weggis, Switzerland, in April 2015, was focused on techniques for the study of normal and cancer stem cells, cell fate decisions, cancer initiation and progression. ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0629-5
更新日期:2015-09-02 00:00:00
abstract:INTRODUCTION:Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) has been shown to enhance breast cancer cell survival and confer resistance to chemotherapeutic agents. We studied the prognostic and predictive value of PIK3CA mutations a...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-014-0405-y
更新日期:2014-07-24 00:00:00
abstract::The mammary gland develops as an appendage of the ectoderm. The prenatal stage of mammary development is hormone independent and is regulated by sequential and reciprocal signaling between the epithelium and the mesenchyme. A number of recent studies using human and mouse genetics, in particular targeted gene deletion...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr776
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:We have previously shown that galactosylceramide (GalCer) affects the tumourigenic and metastatic properties of breast cancer cells by acting as an anti-apoptotic molecule. Since GalCer is a precursor molecule in the synthesis of sulfatides, the present study was aimed to define the role of sulfatides in apo...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-1058-z
更新日期:2018-11-06 00:00:00
abstract:INTRODUCTION:The neuron-glial antigen 2 (NG2) proteoglycan promotes pericyte recruitment and mediates pericyte interaction with endothelial cells. In the absence of NG2, blood vessel development is negatively impacted in several pathological models. Our goal in this study was to determine the effect of NG2 ablation on ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3174
更新日期:2012-04-24 00:00:00
abstract:INTRODUCTION:Mammographic density is one of the strongest risk factors for breast cancer and is believed to represent epithelial and stromal proliferation. Because of the high heritability of breast density, and the role of the insulin-like growth factor (IGF) pathway in cellular proliferation and breast development, w...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1655
更新日期:2007-01-01 00:00:00
abstract::This cross-sectional investigation in Hawaii explored the relation between soy foods and mammographic characteristics using two food frequency questionnaires and a computer-assisted density assessment method. Japanese and Chinese women reported significantly greater soy food intake than Caucasian women. Whereas soy in...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr285
更新日期:2001-01-01 00:00:00
abstract:INTRODUCTION:PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α) somatic mutations are the most common genetic alteration in breast cancer (BC). Their prognostic value and that of the phosphatidylinositol 3-kinase (PI3K) pathway in BC remains only partly defined. The effect of PIK3CA mutations ...
journal_title:Breast cancer research : BCR
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/bcr3683
更新日期:2014-06-30 00:00:00
abstract:INTRODUCTION:Metastasis of breast cancer is the main cause of death in patients. Previous genome-wide studies have identified gene-expression patterns correlated with cancer patient outcome. However, these were derived mostly from whole tissue without respect to cell heterogeneity. In reality, only a small subpopulatio...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3344
更新日期:2012-10-31 00:00:00
abstract::Targeting the function of epidermal growth factor receptor (EGFR) has failed as an effective clinical option for breast cancer. Understanding the drivers of inherent resistance has been a challenge. One possible mechanism is the acquisition of stem-like properties through the process of epithelial-mesenchymal transiti...
journal_title:Breast cancer research : BCR
pub_type: 评论,杂志文章
doi:10.1186/s13058-014-0448-0
更新日期:2014-09-23 00:00:00
abstract:BACKGROUND:We previously performed a case-control genome-wide association study in women treated with selective estrogen receptor modulators (SERMs) for breast cancer prevention and identified single nucleotide polymorphisms (SNPs) in ZNF423 as potential biomarkers for response to SERM therapy. The ZNF423rs9940645 SNP,...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0890-x
更新日期:2017-08-18 00:00:00
abstract:BACKGROUND:Developing novel strategies against treatment-resistant triple negative breast cancer (TNBC) cells remains a significant challenge. The ErbB family, including epidermal growth factor receptor (EGFR), plays key roles in metastasis, tumorigenesis, cell proliferation, and drug resistance. Recently, these charac...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0662-4
更新日期:2016-01-12 00:00:00
abstract:INTRODUCTION:Breast cancers frequently metastasise to the skeleton where they cause osteolytic bone destruction by stimulating osteoclasts to resorb bone and by preventing osteoblasts from producing new bone. The Runt-related transcription factor 2, Runx2, is an important determinant of bone metastasis in breast cancer...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3048
更新日期:2011-10-27 00:00:00
abstract:BACKGROUND:The oncogenic receptor tyrosine kinase (RTK) ERBB2 is known to dimerize with other EGFR family members, particularly ERBB3, through which it potently activates PI3K signalling. Antibody-mediated inhibition of this ERBB2/ERBB3/PI3K axis has been a cornerstone of treatment for ERBB2-amplified breast cancer pat...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-019-1127-y
更新日期:2019-03-21 00:00:00
abstract:BACKGROUND:MicroRNAs (miRNAs) regulate gene expression and influence cancer. Primary transcripts of miRNAs (pri-miRNAs) are poorly annotated and little is known about the role of germline variation in miRNA genes and breast cancer (BC). We sought to identify germline miRNA variants associated with BC risk and tumor sub...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0964-4
更新日期:2018-06-05 00:00:00
abstract::For the past 20 years the mouse has served as a workhorse for studying the molecular underpinnings of human breast cancer. While some genetically engineered mouse mammary tumor models do not accurately recapitulate human disease (that is, the MMTV-Neu model and HER2-overexpressing human cancers), additional tumor mode...
journal_title:Breast cancer research : BCR
pub_type: 评论,社论
doi:10.1186/bcr2569
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:There is a growing interest in delivering more personalised, risk-based breast cancer screening protocols. This requires population-level validation of practical models that can stratify women into breast cancer risk groups. Few studies have evaluated the Gail model (NCI Breast Cancer Risk Assessment Tool) i...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-1084-x
更新日期:2018-12-20 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::The key to optimising our approach in early breast cancer is to individualise care. Each patient has a tumour with innate features that dictate their chance of relapse and their responsiveness to treatment. Often patients with similar clinical and pathological tumours will have markedly different outcomes and response...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr2238
更新日期:2009-01-01 00:00:00
abstract::A small proportion of breast cancers are due to a heritable predisposition. Recently, two predisposition genes, BRCA1 and BRCA2, have been identified and cloned. The morphological features of tumours from patients harbouring mutations in the BRCA1 and BRCA2 genes differ from each other and from sporadic breast cancers...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr10
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND:Several anthropometric measures have been found to be associated with the risk of breast cancer. Current weight, body mass index, and adult weight gain appear to be predictors of postmenopausal breast cancer. These factors have been associated with a reduced risk of premenopausal breast cancer. We asked whet...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1293
更新日期:2005-01-01 00:00:00
abstract::The European Network for Breast Development and Cancer (ENBDC) Workshop on ‘Methods in Mammary Gland Development and Cancer’ has grown into the essential, international technical discussion forum for scientists with interests in the normal and neoplastic breast. The fifth ENBDC meeting was held in Weggis, Switzerland ...
journal_title:Breast cancer research : BCR
pub_type:
doi:10.1186/bcr3497
更新日期:2013-01-01 00:00:00
abstract::Many women newly diagnosed with breast cancer and with a strong family history of breast cancer are referred to a family cancer service for genetic counselling and for consideration of genetic testing for germline mutations in cancer predisposition genes following completion of their cancer treatment. However, there i...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr2194
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:Microtubule-associated protein tau (MAPT) inhibits the function of taxanes and high expression of MAPT decreases the sensitivity to taxanes. The relationship between estrogen receptor (ER) and MAPT in breast cancer is unclear. In this study, we examined the correlation of MAPT expression with the sensitivi...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2598
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Breast cancer researchers use cell lines to model myriad phenomena ranging from DNA repair to cancer stem cell phenotypes. Though appropriate, and even requisite, for many studies, the suitability of cell lines as tumour models has come into question owing to possibilities of tissue culture artefacts and c...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0613-0
更新日期:2015-08-20 00:00:00
abstract:BACKGROUND:An increasing number of women are evaluated for potential breast cancer and may experience mental distress during evaluation. We aim to assess the risks of psychiatric disorders and cardiovascular diseases during the diagnostic workup of potential breast cancer. METHODS:All women with a new diagnosis of uns...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-019-1232-y
更新日期:2019-12-10 00:00:00