Abstract:
:We investigated the role of glial cell line-derived neurotrophic factor (GDNF) in compensating trastuzumab (TZMB)-induced apoptosis in HER2+ breast cancer (BC) cells using xenograft tumors. We generated BC xenografts in nude mice using samples from three patients selected based on their HER2 status and response to TZMB therapy. TZMB treatment resulted in shrinkage of the HER2+ TZMB-sensitive xenograft tumor but not the HER2- or HER2+ TZMB-resistant ones. GDNF neutralized TZMB activity and induced growth in all tumors. Three distinct cell lines were derived from these tumors and named, respectively, TZMB-sensitive (TSTC), HER2- (HNTC), and TZMB-resistant (TRTC). Over 50% of TRTC but 1% of TSTC cells expressed CD44, whereas 84% of TSTC were CD24+ compared to only 1% of TRTC, despite comparable levels of HER2 detected in both. TZMB induced profound morphological changes toward apoptosis in TSTC but not in TRTC or HNTC. However, GDNF significantly compensated TZMB-mediated TSTC cell loss and promoted growth by 37 and 50%, respectively, in TSTC and TRTC. Inhibition of SRC by Saracatinib (SARC) blocked GDNF function and accelerated TZMB-mediated cell death in TSTC, but GDNF continued promoting TRTC growth. These changes paralleled with expression levels of the key molecules involved in growth and apoptosis. Collectively, we found in our xenograft samples that firstly SRC mediates GDNF pro-survival functions by bridging RET-HER2 crosstalk in TZMB-responsive BC tumors. Secondly, SARC-TZMB interactions can synergistically eradicate such tumor cells; and thirdly, GDNF can support antibody resistance by acting independent from SRC in tumors with poor HER2 response to TZMB therapy.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Gardaneh M,Shojaei S,Kaviani A,Behnam Bdoi
10.1007/s10549-016-4078-3subject
Has Abstractpub_date
2017-04-01 00:00:00pages
231-241issue
2eissn
0167-6806issn
1573-7217pii
10.1007/s10549-016-4078-3journal_volume
162pub_type
杂志文章abstract::Triple negative breast cancer (TNBC) is an aggressive clinical phenotype characterized by lack of expression (or minimal expression) of estrogen receptor (ER) and progesterone receptor (PR) as well as an absence of human epidermal growth factor receptor-2 (HER2) overexpression. It shows substantial overlap with basal-...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-010-1293-1
更新日期:2011-02-01 00:00:00
abstract::The clinical benefit of eribulin versus capecitabine was evaluated using health-related quality of life (HRQoL) data from a phase 3 randomized trial in patients with pretreated advanced/metastatic breast cancer (ClinicalTrials.gov identifier: NCT00337103). The study population has been described previously (Kaufman et...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s10549-015-3633-7
更新日期:2015-12-01 00:00:00
abstract::Steroid receptor coactivators are important in regulating the function of the receptors in endocrine organ development and in cancers, including breast. Androgen receptor (AR) coactivator ARA70, was first identified as a gene fused to the ret oncogene and later characterized as an AR coactivator. We previously reporte...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1131-5
更新日期:2011-07-01 00:00:00
abstract::Photodynamic therapy (PDT) is a minimally invasive, FDA-approved therapy for treatment of endobronchial and esophageal cancers that are accessible to light. Inflammatory breast cancer (IBC) is an aggressive and highly metastatic form of breast cancer that spreads to dermal lymphatics, a site that would be accessible t...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3618-6
更新日期:2015-11-01 00:00:00
abstract::M1775R and A1789T are two missense variants located within the BRCT domains of BRCA1 gene. The M1775R is a known deleterious variant, while the A1789T is an unclassified variant that has been analyzed and classified as probably deleterious for the first time by our group. In a previous study, we described the expressi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2705-9
更新日期:2013-10-01 00:00:00
abstract:BACKGROUND:The purpose of this retrospective study was to analyze the overall survival of patients with brain metastases due to breast cancer and to identify prognostic factors that affect clinical outcome. METHODS:Of the 7,872 breast cancer patients histologically diagnosed with breast cancer between January 1990 and...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9806-2
更新日期:2008-10-01 00:00:00
abstract:PURPOSE:To evaluate the loco-regional recurrence (LRR) rate after breast-conserving surgery without postoperative radiotherapy (RT) for ductal carcinoma in situ (DCIS) of the breast. METHODS:Between 2000 and 2010, 311 DCIS patients from 9 institutions were analyzed retrospectively. The median age was 47 (range, 20-82)...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
doi:10.1007/s10549-017-4111-1
更新日期:2017-02-01 00:00:00
abstract::Platinum agents such as cisplatin and carboplatin are DNA-damaging agents with activity in breast cancer (BC), particularly in the triple negative (TN) subgroup. The utility of platinum agents, in addition to standard neoadjuvant chemotherapy (NAC), is controversial. To assess the activity of platinum agents in patien...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10549-014-2876-z
更新日期:2014-04-01 00:00:00
abstract::The effect of estradiol (E2) on the [3H]-acetylation of nuclear histones was studied in the MCF-7 human mammary cancer cell line in culture. Cells (approximately 10(8) were incubated with 8 x 10(-6) M [3H]-acetate in the absence (control) or in the presence of estradiol (10(-5)-10(-8) M). After 20 min incubation, the ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01805980
更新日期:1989-10-01 00:00:00
abstract::Node-positive breast carcinoma is an aggressive disease. Postmenopausal patients benefit from antiestrogen adjuvant therapy. Predictive markers could, however, be useful in selecting these patients for different modalities of adjuvant therapy. Recently, we showed that MMP-2 (72 kD type IV collagenase/gelatinase A) is ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006458601568
更新日期:2001-01-01 00:00:00
abstract::Complete remissions in patients with metastatic breast cancer using endocrine therapy or chemotherapy are infrequent. Breast tumors are known to be heterogeneous with respect to estrogen receptor status, and the low complete remission rate may be related to this biochemical heterogeneity. Based on laboratory experimen...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01805721
更新日期:1982-01-01 00:00:00
abstract::The specific role of dietary fat in breast cancer progression is unclear, although a low-fat diet was associated with decreased recurrence of estrogen receptor alpha negative (ER(-)) breast cancer. ER(-) basal-like MDA-MB-231 and MDA-MB-436 breast cancer cell lines contained a greater number of cytoplasmic lipid dropl...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-009-0594-8
更新日期:2010-08-01 00:00:00
abstract::WWOX is a cancer gene, spanning the common chromosomal fragile site 16D. Genomic and expression aberrations affecting this gene and locus are common in various neoplasias including breast cancer. The aim of the present study was to evaluate the relationship between WWOX expression at the protein level with respect to ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-004-1474-x
更新日期:2005-01-01 00:00:00
abstract::The tumor-stroma ratio has previously been shown to be prognostic for patients with invasive breast cancer. We present a validation study to assess the prognostic significance in lymph node-negative, premenopausal patients from the perioperative chemotherapy trial (POP trial, 10854) conducted by the European Organizat...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2571-5
更新日期:2013-06-01 00:00:00
abstract::We calculated hazard rates for recurrence in patients with primary breast cancer (stage I, II; no adjuvant therapy). Previous publications have indicated a peak in hazard rates for recurrence (or death) at approximately 2-3 years after diagnosis of primary breast cancer. However, there have been conflicting reports co...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-004-1722-0
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:TOP2A gene encodes topoisomerase II alpha, the direct molecular target of anthracyclines. This gene is frequently coamplified with HER2. The aims of this study were to analyse the pattern of TOP2A amplification and protein expression in relation to the molecular subgroups of breast cancers; and to define the...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-006-9492-5
更新日期:2007-12-01 00:00:00
abstract::Animal models have contributed to our understanding of breast cancer, with publication of results in high-impact journals almost invariably requiring extensive in vivo experimentation. As such, many laboratories hold large collections of surplus animal material, with only a fraction being used in publications relating...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3785-0
更新日期:2016-04-01 00:00:00
abstract::Our aim was to develop an accurate diagnostic system using gene expression analysis by means of DNA microarray for prognosis of node-negative and estrogen receptor (ER)-positive breast cancer patients in order to identify a subset of patients who can be safely spared adjuvant chemotherapy. A diagnostic system comprisi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1145-z
更新日期:2011-08-01 00:00:00
abstract::There are increasing evidences that HSD17B1 plays a significant role in the development of breast cancer. However, published data on the association between HSD17B1 Ser312Gly polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of this relationship, a meta-analysis includi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析
doi:10.1007/s10549-010-0784-4
更新日期:2010-09-01 00:00:00
abstract::Monitoring effective antiestrogenic activity of the triphenylethylenes in patients with breast cancer is usually determined by the duration of response. The pharmacokinetics of toremifene and tamoxifen have been shown to be highly variable but patient specific. In the present study, we developed a method to accurately...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01832356
更新日期:1992-01-01 00:00:00
abstract::Fibroblast growth factor receptor 2 is a tyrosine kinase receptor that is a member of the family of individually distinct fibroblast growth factor receptors involved in cell proliferation, invasiveness, motility, and angiogenesis. Genome-wide association studies have identified FGFR2 as a breast cancer (BC) susceptibi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析
doi:10.1007/s10549-010-0872-5
更新日期:2010-11-01 00:00:00
abstract:OBJECTIVES:To determine any changes in usage of axillary dissection over time from 1983 to 1993, and to characterize those patients who do not receive axillary node dissection. METHODS:A total of 129,946 female patients receiving cancer-directed surgery for early stage breast cancer, who were identified from the SEER ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006170811237
更新日期:1999-01-01 00:00:00
abstract::Droloxifene, a new antiestrogen, has theoretical advantages over tamoxifen based on preclinical data. These include higher affinity to the estrogen receptor, higher antiestrogenic to estrogenic ratio, and more effective inhibition of cell growth and division in ER positive cell lines, as well as less toxicity, includi...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/BF00689679
更新日期:1994-01-01 00:00:00
abstract::The relationships between urinary 11-desoxy-17-oxo steroids (11-DOS), the ratio of 11-DOS to urinary 17-hydroxycorticosteroids (urinary discriminant ratio), plasma levels of the adrenal androgens dehydroepiandrosterone (DHA), DHA sulphate (DHAS), and 7 alpha-hydroxy DHA (7 alpha DHA), and tumour oestrogen receptor (ER...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00665771
更新日期:1994-01-01 00:00:00
abstract::The biological and clinical significance of circulating tumor cells (CTC) in the peripheral blood of breast cancer patients is not known. To study this question, we used a direct visualization assay to correlate the number of CTC with disease stage and progression. The CTC were enriched from the nucleated cell fractio...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/B:BREA.0000036897.92513.72
更新日期:2004-08-01 00:00:00
abstract::The malignant biological behavior of breast cancer remains obscure on diagnostic images, although understanding the grade of such malignancy is important for selecting appropriate treatment. Therefore, malignancy grades in operable breast cancer were evaluated using positron emission tomography/computed tomography (PE...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
doi:10.1007/s10549-013-2687-7
更新日期:2013-09-01 00:00:00
abstract::Aberrant expressions of the neuronal protein synuclein gamma (SNCG) in malignant mammary epithelial cells are strongly associated with the progression of breast cancer. SNCG is not expressed in normal breast tissues but abundantly expressed in a high percentage of invasive and metastatic breast carcinomas. Several stu...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-005-6938-0
更新日期:2005-11-01 00:00:00
abstract::Multiple adjuvant regimens are used for HER2+ breast cancer, but experience in routine practice is not reported. We evaluated whether oncologists' perceptions of these regimens matches clinical experience. We surveyed Wisconsin medical oncologists throughout the state regarding factors impacting selection of TCH (doce...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1862-y
更新日期:2012-01-01 00:00:00
abstract::Local formation of estradiol in human breast tumors could provide a more important source of estrogen than is delivered from plasma. Prior studies have suggested that estrone is primarily synthesized from estrone sulfate. The enzyme 17 beta-hydroxysteroid dehydrogenase (HSD) would be required to convert estrone to est...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01886734
更新日期:1986-01-01 00:00:00
abstract::The enumeration of circulating tumor cells (CTCs) provides important prognostic values in patients with metastatic breast cancer. Recent studies indicate that individual CTCs form clusters and these CTC-clusters play an important role in tumor metastasis. We aimed to assess whether quantification of CTC-clusters provi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3636-4
更新日期:2015-12-01 00:00:00