Abstract:
INTRODUCTION:Treatment with estrogen and progesterone (E+P) mimics the protective effect of parity on mammary tumors in rodents and depends upon the activity of p53. The following experiments tested whether exogenous E+P primes p53 to be more responsive to DNA damage and whether these pathways confer resistance to mammary tumors in a mouse model of Li-Fraumeni syndrome. METHODS:Mice that differ in p53 status (Trp53+/+, Trp53+/-, Trp53-/-) were treated with E+P for 14 days and then were tested for p53-dependent responses to ionizing radiation. Responses were also examined in parous and age-matched virgins. The effects of hormonal exposures on tumor incidence were examined in BALB/c-Trp53+/- mammary tissues. RESULTS:Nuclear accumulation of p53 and apoptotic responses were increased similarly in the mammary epithelium from E+P-treated and parous mice compared with placebo and age-matched virgins. This effect was sustained for at least 7 weeks after E+P treatment and did not depend on the continued presence of ovarian hormones. Hormone stimulation also enhanced apoptotic responses to ionizing radiation in BALB/c-Trp53+/- mice but these responses were intermediate compared with Trp53+/+ and Trp-/- tissues, indicating haploinsufficiency. The appearance of spontaneous mammary tumors was delayed by parity in BALB/c-Trp53+/- mice. The majority of tumors lacked estrogen receptor (ER), but ER+ tumors were observed in both nulliparous and parous mice. However, apoptotic responses to ionizing radiation and tumor incidence did not differ among outgrowths of epithelial transplants from E+P-treated donors and nulliparous donors. CONCLUSION:Therefore, E+P and parity confer a sustained increase in p53-mediated apoptosis within the mammary epithelium and suppress mammary tumorigenesis, but this effect was not retained in epithelial outgrowths.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Dunphy KA,Blackburn AC,Yan H,O'Connell LR,Jerry DJdoi
10.1186/bcr2094subject
Has Abstractpub_date
2008-01-01 00:00:00pages
R43issue
3eissn
1465-5411issn
1465-542Xpii
bcr2094journal_volume
10pub_type
杂志文章abstract:INTRODUCTION:Human epidermal growth factor receptor-2 (HER2) gene amplification (HER2+) drives tumor cell growth and survival in ~25% of breast cancers. HER2 signaling activates the type I phosphoinositide 3-kinase (PI3K), upon which these tumors rely. Consequently, inhibitors of HER2 and type I PI3K block growth and i...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0656-2
更新日期:2015-12-04 00:00:00
abstract::Therapeutic choices for metastatic tumors are, in most cases, based upon the histological and molecular analysis of the corresponding primary tumor. Understanding whether and to what extent the genomic landscape of metastasis differs from the tumors from which they originated is critical yet largely unknown. A recent ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2469
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Full-field digital mammography (FFDM) has largely replaced film-screen mammography in the US. Breast density assessed from film mammograms is strongly associated with breast cancer risk, but data are limited for processed FFDM images used for clinical care. METHODS:We conducted a case-control study nested a...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-016-0715-3
更新日期:2016-05-21 00:00:00
abstract:BACKGROUND:Breast cancer is a highly heterogeneous disease characterized by multiple histologic and molecular subtypes. While a myriad of breast cancer cell lines have been developed over the past 60 years, estrogen receptor alpha (ER)+ disease and some mutations associated with this subtype remain underrepresented. He...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01300-y
更新日期:2020-06-23 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:INTRODUCTION:The main prognostic variables in early breast cancer are tumor size, histological grade, estrogen receptor/progesterone receptor (ER/PgR) status, number of positive nodes and human epidermal growth factor receptor 2 (HER2) status. The present study evaluated the prognostic and/or predictive value of vascul...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,随机对照试验
doi:10.1186/bcr3354
更新日期:2012-11-12 00:00:00
abstract::Testosterone binds to the androgen receptor in target tissue to mediate its effects. Variations in testosterone levels and androgen receptor activity may play a role in the etiology of breast cancer. Here, we review the epidemiologic evidence linking endogenous testosterone to breast cancer risk. Paradoxically, result...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr593
更新日期:2003-01-01 00:00:00
abstract::STATEMENT OF FINDINGS: We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses' Health Study cohort. We observed no association between AIB1 genotype and breast cancer incidence, or specific tumor char...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr82
更新日期:2000-01-01 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::Certain laminins of vascular basement membranes have been identified in human breast tumors and brain gliomas that share the same beta1 chain. These laminins are new carcinoma angiogenic markers and might represent potential targets for antiangiogenic therapy. ...
journal_title:Breast cancer research : BCR
pub_type: 评论,杂志文章
doi:10.1186/bcr1270
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Breast ductal carcinoma in situ (DCIS) represent approximately 20% of screen-detected breast cancers. The overall risk for DCIS patients treated with breast-conserving surgery stems almost exclusively from local recurrence. Although a mastectomy or adjuvant radiation can reduce recurrence risk, there are sig...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-019-1165-5
更新日期:2019-07-29 00:00:00
abstract:BACKGROUND:The global observational BREAKOUT study investigated germline BRCA mutation (gBRCAm) prevalence in a population of patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). METHODS:Eligible patients had initiated first-line cytotoxic chemotherapy for HER2-negativ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究
doi:10.1186/s13058-020-01349-9
更新日期:2020-10-27 00:00:00
abstract::Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that is effective and generally well tolerated when administered as a single agent to treat advanced breast cancer. Efficacy has now been demonstrated in randomized trials as first line, second line, and later than the second line treatment of advanced breast...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr3621
更新日期:2014-03-05 00:00:00
abstract::The Developmental Origins of Health and Disease (DOHaD) theory focuses on the consequences of periconceptional and in utero exposures. A wide range of environmental conditions during early development are now being investigated as a driving force for epigenetic disruptions that enhance disease risk in later life, incl...
journal_title:Breast cancer research : BCR
pub_type: 评论,社论
doi:10.1186/s13058-016-0760-y
更新日期:2016-10-12 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:INTRODUCTION:Triple-negative breast cancer (TNBC) is a subtype of highly malignant breast cancer with poor prognosis. TNBC is not amenable to endocrine therapy and often exhibit resistance to current chemotherapeutic agents, therefore, further understanding of the biological properties of these cancer cells and develop...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-014-0434-6
更新日期:2014-09-11 00:00:00
abstract:BACKGROUND:Tumor hypoxia is an independent prognostic factor associated with poor patient survival. Emerging evidence suggests that hypoxia can potentially maintain or enhance the stem cell phenotype of both normal stem cells and cancer cells. However, it remains to be determined whether cell fate is regulated in vivo ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0944-8
更新日期:2018-03-06 00:00:00
abstract::The potential for a reduction in dietary fat or for an increase in dietary fiber to reduce breast cancer risk has been debated for some years. It is argued here that available research data, even though extensive, leave open hypotheses ranging from little or no potential to major public health potential for breast can...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr68
更新日期:2000-01-01 00:00:00
abstract:INTRODUCTION:Molecular dissection of the signaling pathways that underlie complex biological responses in the mammary epithelium is limited by the difficulty of propagating large numbers of mouse mammary epithelial cells, and by the inability of ribonucleic acid interference (RNAi)-based knockdown approaches to fully a...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2728
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:We present a fully automated method for deriving quantitative measures of background parenchymal enhancement (BPE) from breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perform a preliminary evaluation of these measures to assess the effect of risk-reducing salpingo-oophorectomy (R...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0577-0
更新日期:2015-05-19 00:00:00
abstract:BACKGROUND:Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry. METHODS:We evaluated 88 breast cancer risk variant...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-016-0786-1
更新日期:2016-12-08 00:00:00
abstract:BACKGROUND:Texture patterns have been shown to improve breast cancer risk segregation in addition to area-based mammographic density. The additional value of texture pattern scores on top of volumetric mammographic density measures in a large screening cohort has never been studied. METHODS:Volumetric mammographic den...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0961-7
更新日期:2018-05-02 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::Following publication of the original article [1], the authors reported a typesetting error in the spelling of the second author's name. ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,已发布勘误
doi:10.1186/s13058-018-1069-9
更新日期:2018-11-19 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: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::Breast cancer is a heterogeneous disease with varied morphological appearances, molecular features, behavior, and response to therapy. Current routine clinical management of breast cancer relies on the availability of robust clinical and pathological prognostic and predictive factors to support clinical and patient de...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr2607
更新日期:2010-01-01 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:Aberrant activation of Wnt/β-catenin signaling plays an important role in the pathogenesis of breast cancer. DACT1 (Dapper/Frodo) has been identified as involved in antagonizing Wnt/β-catenin signaling through interacting with Dishevelled (Dvl), a central mediator of Wnt signaling, whereas its role in brea...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3399
更新日期:2013-03-12 00:00:00
abstract:BACKGROUND:A novel line of research suggests that eating at nighttime may have several metabolic consequences that are highly relevant to breast cancer. We investigated the association between nighttime eating habits after 10 p.m. and breast cancer in Hong Kong women. METHODS:A hospital-based case-control study was co...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0821-x
更新日期:2017-03-17 00:00:00