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-negative breast cancer cell lines (HCC-1937, MDA-MB-231, MDA-MB-468, MDA-MB-453 and SK-BR-3) were used for in vitro studies. Cellular apoptosis was examined by flow cytometry and Western blot analysis. Signal transduction pathways in cells were assessed by Western blot analysis. The in vivo efficacy of tamoxifen was tested in xenograft nude mice. RESULTS:Tamoxifen induced significant apoptosis in MDA-MB-231, MDA-MB-468, MDA-MB-453 and SK-BR-3 cells, but not in HCC-1937 cells. Tamoxifen-induced apoptosis was associated with inhibition of cancerous inhibitor of protein phosphatase 2A (CIP2A) and phospho-Akt (p-Akt) in a dose-dependent manner. Ectopic expression of either CIP2A or Akt protected MDA-MB-231 cells from tamoxifen-induced apoptosis. In addition, tamoxifen increased protein phosphatase 2A (PP2A) activity, and tamoxifen-induced apoptosis was attenuated by the PP2A antagonist okadaic acid in the sensitive cell lines, but not in resistant HCC-1937 cells. Moreover, silencing CIP2A by small interfering RNA sensitized HCC-1937 cells to tamoxifen-induced apoptosis. Furthermore, tamoxifen regulated CIP2A protein expression by downregulating CIP2A mRNA. Importantly, tamoxifen inhibited the in vivo growth of MDA-MB-468 xenograft tumors in association with CIP2A downregulation, whereas tamoxifen had no significant effect on CIP2A expression and anti-tumor growth in HCC-1937 tumors. CONCLUSIONS:Inhibition of CIP2A determines the effects of tamoxifen-induced apoptosis in ER-negative breast cancer cells. Our data suggest a novel "off-target" mechanism of tamoxifen and suggest that CIP2A/PP2A/p-Akt signaling may be a feasible anti-cancer pathway.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Liu CY,Hung MH,Wang DS,Chu PY,Su JC,Teng TH,Huang CT,Chao TT,Wang CY,Shiau CW,Tseng LM,Chen KFdoi
10.1186/s13058-014-0431-9subject
Has Abstractpub_date
2014-09-17 00:00:00pages
431issue
5eissn
1465-5411issn
1465-542Xpii
s13058-014-0431-9journal_volume
16pub_type
杂志文章abstract::Estrogen receptor α (ER) is a major driver of breast cancer and the target of endocrine therapy. Full disclosure of the cofactors regulating ER interactions with chromatin and its transcriptional regulatory activity is still elusive. Novel genome-wide profiling tools have mapped ER binding events in breast cancer cell...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2849
更新日期:2011-04-20 00:00:00
abstract::Transforming growth factor-beta (TGF-beta) is a tumor suppressor, the function of which is compromised in many types of human cancer, including breast cancer. The tumor suppressive effects of TGF-beta are caused by potent inhibition of cell proliferation due to cell cycle arrest in the G1 phase. Such antiproliferative...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr42
更新日期:2000-01-01 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:The purpose of this work was to study the prognostic influence in breast cancer of thioredoxin reductase 1 (TXNRD1) and thioredoxin interacting protein (TXNIP), key players in oxidative stress control that are currently evaluated as possible therapeutic targets. METHODS:Analysis of the association of TXNR...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究
doi:10.1186/bcr2599
更新日期:2010-01-01 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:BACKGROUND:Chemotherapy is the standard treatment for breast cancer; however, the response to chemotherapy is disappointingly low. Here, we investigated the alternative therapeutic efficacy of novel combination treatment with necroptosis-inducing small molecules to overcome chemotherapeutic resistance in tyrosine amino...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01367-7
更新日期:2020-11-25 00:00:00
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: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 ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2754
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:Rapamycin, an inhibitor of the serine/threonine kinase target of rapamycin, induces G1 arrest and/or apoptosis. Although rapamycin and its analogues are attractive candidates for cancer therapy, their sensitivities with respect to growth inhibition differ markedly among various cancer cells. Using human br...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1344
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Breast cancers can be classified using whole genome expression into distinct subtypes that show differences in prognosis. One of these groups, the basal-like subtype, is poorly differentiated, highly metastatic, genomically unstable, and contains specific genetic alterations such as the loss of tumour prot...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2142
更新日期:2008-01-01 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:INTRODUCTION:Bisphosphonates have become standard therapy for the treatment of skeletal complications related to breast cancer. Although their therapeutic effects mainly result from an inhibition of osteoclastic bone resorption, in vitro data indicate that they also act directly on breast cancer cells, inhibiting proli...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1845
更新日期:2008-01-01 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:Incidence of breast cancer is increasing around the world and it is still the leading cause of cancer mortality in low- and middle-income countries. We utilized Swedish nationwide registers to study breast cancer incidence and case fatality to disentangle the effect of socioeconomic position (SEP) and immi...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3086
更新日期:2012-01-06 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: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:Mammary-specific overexpression of Six1 in mice induces tumors that resemble human breast cancer, some having undergone epithelial to mesenchymal transition (EMT) and exhibiting stem/progenitor cell features. Six1 overexpression in human breast cancer cells promotes EMT and metastatic dissemination. We hyp...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3219
更新日期:2012-07-05 00:00:00
abstract:INTRODUCTION:The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) is a multidisciplinary, collaborative framework for the investigation of familial breast cancer. Based in Australia, the primary aim of kConFab is to facilitate high-quality research by amassing a large and comp...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1377
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:With the improvement of therapeutic options for the treatment of breast cancer, the development of brain metastases has become a major limitation to life expectancy in many patients. Therefore, our aim was to identify molecular markers associated with the development of brain metastases in breast cancer. ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3150
更新日期:2012-03-19 00:00:00
abstract:INTRODUCTION:The ataxia-telangiectasia mutated (ATM) gene (MIM ID 208900) encodes a protein kinase that plays a significant role in the activation of cellular responses to DNA double-strand breaks through subsequent phosphorylation of central players in the DNA damage-response pathway. Recent studies have confirmed tha...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究
doi:10.1186/bcr2919
更新日期:2011-07-25 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 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: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::Immunohistochemistry is the most common method for companion diagnostic testing in breast cancer. The readings for estrogen receptor, progesterone receptor, and Her2 directly affect prescription of critical therapies. However, immunohistochemistry is highly sensitive to innumerable pre-analytic variables that result i...
journal_title:Breast cancer research : BCR
pub_type: 社论
doi:10.1186/bcr2782
更新日期:2010-01-01 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::Proteins belonging to the profilin family of actin-binding proteins are considered to be important control elements for actin polymerization and have been linked to a broad spectrum of cellular functions, including cell migration. An intriguing paper recently published in Cancer Cell unveils differential effects of pr...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3433
更新日期:2013-06-27 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: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::Recent insights into the molecular and cellular mechanisms underlying cancer development have revealed that immune cells functionally regulate epithelial cancer development and progression. Moreover, accumulated clinical and experimental data indicate that the outcome of an immune response toward an evolving breast ne...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr1746
更新日期:2007-01-01 00:00:00