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 proliferation and inducing apoptosis. METHODS:The present study examined the effects of calcium (from 0.6 to 2.0 mmol/l) on the antitumour activity of the bisphosphonate ibandronate (1 to 1,000 nmol/l) on MDA-MB-231 and MCF-7 breast cancer cells. Cell culture densities were determined using crystal violet staining assay. Apoptotic cell death was assessed by annexin V-phycoerythrin and 7-amino-actinomycin double staining. RESULTS:At low calcium concentration, 30 micromol/l ibandronate had no effect on MDA-MB-231 cells growth and only slightly inhibited MCF-7 cells growth. Higher calcium levels significantly increased growth inhibition as well as cell apoptosis induced by ibandronate. We observed similar effects with zoledronic acid. Of note, enhancement of ibandronate-induced growth inhibition was also observed in other breast cancer cell lines (T-47D, ZR-75, Hs-578T and BT-549 cells). The growth inhibitory effect of ibandronate in the presence of high concentrations of calcium was partly suppressed by the calcium chelator EGTA (ethylene glycol tetra-acetic acid). In addition, in the presence of calcium at high concentrations, cells accumulated more [14C]ibandronate than at low calcium concentrations. We obtained further evidence of enhancement of cellular ibandronate accumulation by calcium by demonstrating that high calcium levels increased the inhibition of protein prenylation induced by the bisphosphonate. CONCLUSION:Altogether, our data suggest that extracellular calcium, probably through its binding to ibandronate, markedly increased its cellular accumulation and its inhibitory activity on breast tumour cells. Thus, calcium released during the process of tumour-induced osteolysis might enhance the antitumour effects of bisphosphonates and contribute to their therapeutic efficacy.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Journé F,Kheddoumi N,Chaboteaux C,Duvillier H,Laurent G,Body JJdoi
10.1186/bcr1845subject
Has Abstractpub_date
2008-01-01 00:00:00pages
R4issue
1eissn
1465-5411issn
1465-542Xpii
bcr1845journal_volume
10pub_type
杂志文章abstract:BACKGROUND:Metastasis is the major cause of death from breast cancer. Colonization and adaption of metastatic cells in distant organs is a rate-limiting step of the cancer spreading. The underlying mechanisms responsible for the colonization of breast cancer to lung metastatic niches are not fully understood. METHODS:...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-019-1114-3
更新日期:2019-02-12 00:00:00
abstract:INTRODUCTION:Breast cancer is the most common female malignancy worldwide and, despite improvements in treatment modalities, there are increased chances of recurrence and metastasis in a substantial number of cases and it remains one of the major causes of mortality among female cancer patients. Anaplastic lymphoma kin...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0610-3
更新日期:2015-09-17 00:00:00
abstract:INTRODUCTION:Insulin-like growth factor binding protein-3 (IGFBP-3) differentially modulates breast epithelial cell growth through insulin-like growth factor (IGF)-dependent and IGF-independent pathways and is a direct (IGF-independent) growth inhibitor as well as a mitogen that potentiates EGF (epidermal growth factor...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr963
更新日期:2005-01-01 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: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::Lobular carcinoma in situ (LCIS) is considered to be a risk factor for the development of invasive breast carcinoma, but it may also be a non-obligate precursor to invasive lobular carcinoma (ILC). Many LCIS lesions do not progress to ILC, and the molecular changes that are necessary for progression from LCIS to ILC a...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/s13058-015-0580-5
更新日期:2015-06-04 00:00:00
abstract::Genome-wide expression microarray studies have revealed that the biological and clinical heterogeneity of breast cancer can be partly explained by information embedded within a complex but ordered transcriptional architecture. Comprising this architecture are gene expression networks, or signatures, reflecting biochem...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr1662
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:Reliable predictive and prognostic markers for routine diagnostic purposes are needed for breast cancer patients treated with neoadjuvant chemotherapy. We evaluated protein biomarkers in a cohort of 116 participants of the GeparDuo study on anthracycline/taxane-based neoadjuvant chemotherapy for operable b...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/bcr2363
更新日期:2009-01-01 00:00:00
abstract::ErbB (also termed HER) receptors are expressed in various tissues of epithelial, mesenchymal and neuronal origin, in which they are involved in the control of diverse biological processes such as proliferation, differentiation, migration and apoptosis. Furthermore, their deregulated expression has been implicated in m...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr327
更新日期:2001-01-01 00:00:00
abstract::A new gene associated with a high risk of breast cancer, termed BRCAX, may exist on chromosome 13q. Tumours from multicase Nordic breast cancer families, in which mutations in BRCA1 and BRCA2 had been excluded, were analyzed using comparative genomic hybridization in order to identify a region of interest, which was a...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr290
更新日期:2001-01-01 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:INTRODUCTION:The chromodomain helicase DNA binding protein 5 (CHD5) has recently been identified as a tumor suppressor in a mouse model. The CHD5 locus at 1p36 is deleted, and its mutation has been detected in breast cancer. We, therefore, evaluated whether CHD5 plays a role in human breast cancer. METHODS:We screened...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3182
更新日期:2012-05-08 00:00:00
abstract:INTRODUCTION:Matrix metalloproteinase (MMP)-2 is very active at degrading extracellular matrix. It is under the influence of an activator, membrane type 1 MMP (MMP-14), and the tissue inhibitor of metalloproteases (TIMP)-2. We hypothesized that the individual expression of these three markers or their balance may help ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1503
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:Breast cancer is genetically and clinically a heterogeneous disease. However, the exact contribution of different cell types and oncogenic mutations to this heterogeneity are not well understood. Recently, we discovered an interaction between Wnt and integrin-linked kinase (ILK) within the signaling cascad...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2592
更新日期:2010-01-01 00:00:00
abstract::The ductal approach to breast cancer, encompassing nipple aspiration, ductal lavage and duct endoscopy, allows assessment of breast ductal epithelial cells and their local microenvironment in a graded process of increasing invasiveness. Samples of ductal epithelial cells sufficient for cytological diagnosis may be saf...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr759
更新日期:2004-01-01 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: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::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:Aberrant expression of the embryonic stem cell marker Sox2 has been reported in breast cancer (BC). We previously identified two phenotypically distinct BC cell subsets separated based on their differential response to a Sox2 transcription activity reporter, namely the reporter-unresponsive (RU) and the mo...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-014-0470-2
更新日期:2014-11-08 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:BACKGROUND:Well-tolerated and commonly used medications are increasingly assessed for reducing breast cancer risk. These include metformin and statins, both linked to reduced hormone availability and cell proliferation or growth and sometimes prescribed concurrently. We investigated independent and joint associations o...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01336-0
更新日期:2020-09-15 00:00:00
abstract:INTRODUCTION:Before any new methodology can be introduced into the routine diagnostic setting it must be technically validated against the established standards. To this end, a ring study involving five international pathology laboratories was initiated to validate chromogenic in situ hybridisation (CISH) against fluor...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究
doi:10.1186/bcr1776
更新日期:2007-01-01 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: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...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3575
更新日期:2013-11-12 00:00:00
abstract:BACKGROUND:CRIPTO is a multi-functional signaling protein that promotes stemness and oncogenesis. We previously developed a CRIPTO antagonist, ALK4L75A-Fc, and showed that it causes loss of the stem cell phenotype in normal mammary epithelia suggesting it may similarly inhibit CRIPTO-dependent plasticity in breast canc...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01361-z
更新日期:2020-11-13 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: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:INTRODUCTION:The majority of breast cancers that occur in BRCA1 mutation carriers (BRCA1 carriers) are estrogen receptor-negative (ER-). Therefore, it has been suggested that ER negativity is intrinsic to BRCA1 cancers and reflects the cell of origin of these tumors. However, approximately 20% of breast cancers that de...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2776
更新日期:2010-01-01 00:00:00
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 mamm...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2094
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:Protein tyrosine kinase 6 (PTK6) is a non-receptor tyrosine kinase that is highly expressed in Human Epidermal Growth Factor 2(+) (Her2(+)) breast cancers. Overexpression of PTK6 enhances anchorage-independent survival, proliferation, and migration of breast cancer cells. We hypothesized that PTK6 inhibiti...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0594-z
更新日期:2015-06-19 00:00:00