Abstract:
INTRODUCTION:Triple-negative breast cancer (TNBC), a subtype of breast cancer with negative expressions of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), is frequently diagnosed in younger women and has poor prognosis for disease-free and overall survival. Due to the lack of known oncogenic drivers for TNBC proliferation, clinical benefit from currently available targeted therapies is limited, and new therapeutic strategies are urgently needed. METHODS:Triple-negative breast cancer cell lines were treated with proteasome inhibitors in combination with lapatinib (a dual epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor). Their in vitro and in vivo viability was examined by MTT assay, clonogenic analysis, and orthotopic xenograft mice model. Luciferase reporter gene, immunoblot, and RT-qPCR, immunoprecipitation assays were used to investigate the molecular mechanisms of action. RESULTS:Our data showed that nuclear factor (NF)-κB activation was elicited by lapatinib, independent of EGFR/HER2 inhibition, in TNBCs. Lapatinib-induced constitutive activation of NF-κB involved Src family kinase (SFK)-dependent p65 and IκBα phosphorylations, and rendered these cells more vulnerable to NF-κB inhibition by p65 small hairpin RNA. Lapatinib but not other EGFR inhibitors synergized the anti-tumor activity of proteasome inhibitors both in vitro and in vivo. Our results suggest that treatment of TNBCs with lapatinib may enhance their oncogene addiction to NF-κB, and thus augment the anti-tumor activity of proteasome inhibitors. CONCLUSIONS:These findings suggest that combination therapy of a proteasome inhibitor with lapatinib may benefit TNBC patients.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Chen YJ,Yeh MH,Yu MC,Wei YL,Chen WS,Chen JY,Shih CY,Tu CY,Chen CH,Hsia TC,Chien PH,Liu SH,Yu YL,Huang WCdoi
10.1186/bcr3575subject
Has Abstractpub_date
2013-11-12 00:00:00pages
R108issue
6eissn
1465-5411issn
1465-542Xpii
bcr3575journal_volume
15pub_type
杂志文章abstract:BACKGROUND:E74-like factor 5 (ELF5) is an epithelial-specific member of the E26 transforming sequence (ETS) transcription factor family and a critical regulator of cell fate in the placenta, pulmonary bronchi, and milk-producing alveoli of the mammary gland. ELF5 also plays key roles in malignancy, particularly in basa...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0666-0
更新日期:2016-01-07 00:00:00
abstract::The concept of 'targeted' therapies implies that such drugs only act on cells that specifically express the particular target, therefore giving rise to a low incidence of side effects. However, targeted therapies currently approved for the treatment of breast cancer have demonstrated a relatively high incidence of car...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr3142
更新日期:2012-06-19 00:00:00
abstract:INTRODUCTION:Recent studies have demonstrated that members of the GATA-binding protein (GATA) family (GATA4 and GATA5) might have pivotal roles in the transcriptional upregulation of mucin genes (MUC2, MUC3 and MUC4) in gastrointestinal epithelium. The zinc-finger GATA3 transcription factor has been reported to be invo...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1617
更新日期:2006-01-01 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: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:Breast cancer is a heterogeneous disease. Hence, stratification of patients based on the subtype of breast cancer is key to its successful treatment. Among all the breast cancer subtypes, basal-like breast cancer is the most aggressive subtype with limited treatment options. Interestingly, we found focal adh...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01298-3
更新日期:2020-06-03 00:00:00
abstract::It is generally accepted that early detection of breast cancer has great impact on patient survival, emphasizing the importance of early diagnosis. In a widely recognized model of breast cancer development, tumor cells progress through chronological and well defined stages. However, the molecular basis of disease prog...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr1528
更新日期:2006-01-01 00:00:00
abstract::Advances in genotyping technology have provided us with a large number of genetic loci associated with cancer susceptibility; however, our ability to understand the functional effects of the genetic variants of these loci remains limited. In the previous issue, Smits and colleagues demonstrate the use of congenic rat ...
journal_title:Breast cancer research : BCR
pub_type: 评论,社论
doi:10.1186/bcr2939
更新日期:2011-10-12 00:00:00
abstract:INTRODUCTION:Human epidermal growth factor 2 (Her2), a receptor tyrosine kinase, is overexpressed in breast cancers. It has been successfully targeted by small molecule kinase inhibitors and by antibodies. Recent clinical data show a synergistic response in patients when two antibodies, trastuzumab and pertuzumab, are ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2888
更新日期:2011-05-22 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::The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatm...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr2111
更新日期:2008-01-01 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:INTRODUCTION:Estrogens play a pivotal role in the initiation and progression of breast cancer. The genes that mediate these processes are not fully defined, but potentially include the known mammary oncogene MYC. Characterization of estrogen-target genes may help to elucidate further the mechanisms of estrogen-induced ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1985
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:Involution of the mammary gland is a complex process of controlled apoptosis and tissue remodelling. The aim of the project was to identify genes that are specifically involved in this process. METHODS:We used Affymetrix oligonucleotide microarrays to perform a detailed transcript analysis on the mechanis...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr753
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Breast cancer stem cells (BCSCs) are typically seed cells of breast tumor that initiate and maintain tumor growth. MiR-7, as a cancer inhibitor, decreases the BCSC subset and inhibits tumor progression through mechanisms that remain unknown. METHODS:We examined miR-7 expression in breast cancer and develope...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01264-z
更新日期:2020-03-06 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:BACKGROUND:Breast cancer intrinsic molecular subtype (IMS) as classified by the expression-based PAM50 assay is considered a strong prognostic feature, even when controlled for by standard clinicopathological features such as age, grade, and nodal status, yet the molecular testing required to elucidate these subtypes i...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-1248-3
更新日期:2020-01-28 00:00:00
abstract::Homeobox (HOX) genes play key roles in embryogenesis and tissue differentiation. Recently, a number of groups have reported altered HOX gene expression in breast cancer. However, the mechanism of HOX gene regulation and the search for direct targets of its transcriptional regulatory function have been minimally fruitf...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2600
更新日期:2010-01-01 00:00:00
abstract::Although the stroma in which carcinomas arise has been previously regarded as a bystander to the clonal expansion and acquisition of malignant characteristics of tumor cells, it is now generally acknowledged that stromal changes are required for the establishment of cancer. In the present article, we discuss three rec...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr972
更新日期:2005-01-01 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:INTRODUCTION:Human epidermal growth factor receptor HER3 has been implicated in promoting the aggressiveness and metastatic potential of breast cancer. Upregulation of HER3 has been found to be a major mechanism underlying drug resistance to EGFR and HER2 tyrosine kinase inhibitors and to endocrine therapy in the treat...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0528-9
更新日期:2015-02-15 00:00:00
abstract::The adaptor protein NHERF1/EBP50 (Na/H exchanger regulatory factor 1/ezrin-radixin-moesin-binding phosphoprotein 50) emerged recently as an important player in breast cancer progression. Consisting of two tandem PDZ domains linked to a carboxyl-terminal ezrin-binding region, NHERF1 assembles macromolecular complexes a...
journal_title:Breast cancer research : BCR
pub_type: 评论,社论
doi:10.1186/bcr1992
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:Tumor cells can effectively be killed by heat, e.g. by using magnetic hyperthermia. The main challenge in the field, however, is the generation of therapeutic temperatures selectively in the whole tumor region. We aimed to improve magnetic hyperthermia of breast cancer by using innovative nanoparticles whi...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0576-1
更新日期:2015-05-13 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:INTRODUCTION:Studies on the association between the cytochrome P450c17alpha gene (CYP17) 5'-untranslated region MspA1 genetic polymorphism and breast cancer risk have yielded inconsistent results. Higher levels of estrogen have been reported among young nulliparous women with the A2 allele. Therefore we assessed the im...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1027
更新日期:2005-01-01 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::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:BACKGROUND:Breast cancer patients with early-stage disease are increasingly administered neoadjuvant chemotherapy (NAC) to downstage their tumors prior to surgery. In this setting, approximately 31% of patients fail to respond to therapy. This demonstrates the need for techniques capable of providing personalized feedb...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01262-1
更新日期:2020-03-13 00:00:00
abstract:INTRODUCTION:Tamoxifen, a selective estrogen receptor (ER) modulator, may affect cancer cell survival through mechanisms other than ER antagonism. In the present study, we tested the efficacy of tamoxifen in a panel of ER-negative breast cancer cell lines and examined the drug mechanism. METHODS:In total, five ER-nega...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-014-0431-9
更新日期:2014-09-17 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