Abstract:
BACKGROUND:One-third of estrogen (ER+) and/or progesterone receptor-positive (PGR+) breast tumors treated with Tamoxifen (TAM) do not respond to initial treatment, and the remaining 70% are at risk to relapse in the future. Estrogen-related receptor gamma (ESRRG, ERRγ) is an orphan nuclear receptor with broad, structural similarities to classical ER that is widely implicated in the transcriptional regulation of energy homeostasis. We have previously demonstrated that ERRγ induces resistance to TAM in ER+ breast cancer models, and that the receptor's transcriptional activity is modified by activation of the ERK/MAPK pathway. We hypothesize that hyper-activation or over-expression of ERRγ induces a pro-survival transcriptional program that impairs the ability of TAM to inhibit the growth of ER+ breast cancer. The goal of the present study is to determine whether ERRγ target genes are associated with reduced distant metastasis-free survival (DMFS) in ER+ breast cancer treated with TAM. METHODS:Raw gene expression data was obtained from 3 publicly available breast cancer clinical studies of women with ER+ breast cancer who received TAM as their sole endocrine therapy. ERRγ target genes were selected from 2 studies that published validated chromatin immunoprecipitation (ChIP) analyses of ERRγ promoter occupancy. Kaplan-Meier estimation was used to determine the association of ERRγ target genes with DMFS, and selected genes were validated in ER+, MCF7 breast cancer cells that express exogenous ERRγ. RESULTS:Thirty-seven validated receptor target genes were statistically significantly altered in women who experienced a DM within 5 years, and could classify several independent studies into poor vs. good DMFS. Two genes (EEF1A2 and PPIF) could similarly separate ER+, TAM-treated breast tumors by DMFS, and their protein levels were measured in an ER+ breast cancer cell line model with exogenous ERRγ. Finally, expression of ERRγ and these two target genes are elevated in models of ER+ breast cancer with hyperactivation of ERK/MAPK. CONCLUSIONS:ERRγ signaling is associated with poor DMFS in ER+, TAM-treated breast cancer, and ESRRG, EEF1A2, and PPIF comprise a 3-gene signaling node that may contribute to TAM resistance in the context of an active ERK/MAPK pathway.
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Madhavan S,Gusev Y,Singh S,Riggins RBdoi
10.1186/s13046-015-0150-9subject
Has Abstractpub_date
2015-05-15 00:00:00pages
45eissn
0392-9078issn
1756-9966pii
10.1186/s13046-015-0150-9journal_volume
34pub_type
杂志文章abstract::Several in vitro and in vivo studies have examined the positive and negative effects of retinoids (vitamin A analogs) in premalignant and malignant lesions. Retinoids have been used as chemopreventive and anticancer agents because of their pleiotropic regulator function in cell differentiation, growth, proliferation a...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/1756-9966-27-18
更新日期:2008-07-14 00:00:00
abstract:BACKGROUND:Annexin A2 is increased in serous ovarian cancer and plays an essential role in ovarian cancer invasion and metastasis. In combination with S100A10, annexin A2 plays an important role in the plasminogen activator system regulating plasmin production. The aim of this study was to investigate the potential uti...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-1017-7
更新日期:2019-01-08 00:00:00
abstract:BACKGROUND:Agonistic CD40 antibodies have been demonstrated to activate antigen-presenting cells (APCs) and enhance antitumour T cell responses, thereby providing a new therapeutic option in cancer immunotherapy. In agonistic CD40 antibody-mediated inflammatory responses, a novel subset of E-cadherin + dendritic cells ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-015-0126-9
更新日期:2015-02-05 00:00:00
abstract::Pretreatment of ethyl acetate extract of Phellinus rimosus (Berk) Pilat protected cisplatin induced nephrotoxicity in mice. Single dose of the extract (25 and 50 mg/kg body weight) decreased cisplatin induced serum creatinine and urea levels. The cisplatin depleted renal antioxidant defence system, such as activity of...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract::We report the long-term results of a series of patients affected by advanced epithelial ovarian cancer treated with the PEC combination (cisplatin 60 mg/m2, epirubicin 60 mg/m2 and cyclophosphamide 750 mg/m2, all at day 1, every 21 days). Response was evaluated after three cycles, and treatment continued in responsive...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract:BACKGROUND:Oncogenic roles of epidermal growth factor receptor pathway substrate no.8 (EPS8) have been widely reported in various tumors, making targeting of EPS8 an appealing prospect. Here, we describe the role of EPS8 in acute myeloid leukemia (AML) and consider the potential of EPS8 as an anti-AML target. Nuclear l...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0682-x
更新日期:2018-01-22 00:00:00
abstract::Gastric tissue was transplanted from the fundic and pyloric mucosa of 8-week old female F344 rats into the duodenum of males. Autopsy, 12 months after the operation, revealed grafts associated with persistent stones in the duodenum and/or calcification in the tissue. Pepsinogen positive chimeric glands with goblet cel...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2000-06-01 00:00:00
abstract:BACKGROUND:Colon cancer represents one of the leading causes of gastrointestinal tumors in industrialized countries, and its incidence appears to be increasing at an alarming rate. Accumulating evidence has unveiled the contributory roles of cancer stem cells (CSCs) in tumorigenicity, recurrence, and metastases. The fu...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01704-w
更新日期:2020-10-28 00:00:00
abstract::Insulin-secreting tumors are the commonest hormone-producing neoplasm of the gastrointestinal tract. They occur with an incidence of 4 cases per million per year. About 10% of them are metastatic and malignant insulinomas very rarely observed in children and in elderly. We report a rare case of very large malignant in...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:
更新日期:2007-12-01 00:00:00
abstract::The presence of NE-differentiation in the follicle-cell thyroid carcinoma has been investigated by immunohistochemical detection of chromogranin A in the neoplastic cells. It has been found that NE-differentiation was present in a significant percentage in the papillary Ca alone (46.60%) whereas all Huerthle-cell neop...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract:BACKGROUND:The evasion of cell death is one of the hallmarks of cancer, contributing to both tumor progression and resistance to therapy. Dedifferentiated and anaplastic thyroid carcinomas that do not take up radioiodine are resistant to conventional anticancer treatments and patients with these tumors are difficult to...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-015-0186-x
更新日期:2015-07-22 00:00:00
abstract:BACKGROUND:Gastric cancer (GC) is one of the most common malignant tumors worldwide. Currently, the overall survival rate of GC is still unsatisfactory despite progress in diagnosis and treatment. Therefore, studying the molecular mechanisms involved in GC is vital for diagnosis and treatment. CircRNAs, a type of nonco...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01791-9
更新日期:2021-01-05 00:00:00
abstract:BACKGROUND:Cancer stem cells (CSCs) are important in the tumorigenesis and progression of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play crucial roles regulating CD133+ and EpCAM+ CSCs in HCC, although it is unclear whether miRNAs regulate CD90+ CSCs in HCC. METHODS:The miRNA profiles of CD90+ and CD90- HCC c...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0452-6
更新日期:2016-11-11 00:00:00
abstract:BACKGROUND:Clinically, prostate cancer (PCa) exhibits a high avidity to metastasize to bone. Myc-associated zinc-finger protein (MAZ) is a well-documented oncogene involved in the progression and metastasis of multiple cancer types, even in PCa. However, the clinical significance and biological roles of MAZ in bone met...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1374-x
更新日期:2019-09-05 00:00:00
abstract:BACKGROUND:Rhein is a lipophilic anthraquinone extensively found in medicinal herbs. Emerging evidence suggests that rhein has significant antitumor effects, supporting its potential use as an antitumor agent. The IL6/STAT3 signaling pathway has been suggested as an attractive target for the discovery of novel cancer t...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-1015-9
更新日期:2019-01-23 00:00:00
abstract:BACKGROUND:MicroRNAs have an important role in diverse biological processes including tumorigenesis. MiR-223 has been reported to be deregulated in several human cancer types. However, its biological role has not been functionally characterized in lung squamous cell carcinoma (LSCC). The following study investigates th...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1079-1
更新日期:2019-02-12 00:00:00
abstract::p21WAF1,CIP1,SDI 1 is a specific inhibitor of cyclin-dependent kinase and a tumor suppressor involved in the pathogenesis of a variety of malignancies. Cdk1/p34cdc2 plays a crucial role during mitosis. The immunoreactivity of p21 WAF1,CIP1,SDI 1 and cdk1/p34cdc2 was evaluated in adenomas and adenocarcinomas of the hum...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2001-12-01 00:00:00
abstract:BACKGROUND:This study was conducted to investigate the expression of CXCR4 in portal vein tumor thrombus (PVTT) tissue and its possible role in the invasiveness of tumor thrombus cells. METHODS:We detected differential expression of CXCR4 between PVTT and hepatocellular carcinoma (HCC) by an immunohistochemical assay....
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-29-156
更新日期:2010-11-27 00:00:00
abstract:BACKGROUND:Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved intracellular mechanism for lysosomal degradation of damaged cellular components. The specific degradation of nuclear components by the autophagy pathway is called nucleophagy. Most studies have focused on autophagic turnover ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1048-8
更新日期:2019-02-11 00:00:00
abstract:BACKGROUND:Growing evidences indicate that circular RNAs (circRNAs) play an important role in the regulation of biological behavior of tumor. We aim to explore the role of circRNA in glioma and elucidate how circRNA acts. METHODS:Real-time PCR was used to examine the expression of circPTN in glioma tissues and normal ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1376-8
更新日期:2019-09-11 00:00:00
abstract:PURPOSE:The association between striking life events, an important stress and acute anxiety disorder, and the occurrence of primary breast cancer is unclear. The current meta-analysis was designed to assess the relationship between striking life events and primary breast cancer incidence in women. METHODS:Systematic c...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,meta分析
doi:10.1186/1756-9966-32-53
更新日期:2013-08-13 00:00:00
abstract:BACKGROUND:Glucose-6-phospate dehydrogenase (G6PD) is the limiting enzyme of the pentose phosphate pathway (PPP) correlated to cancer progression and drug resistance. We previously showed that G6PD inhibition leads to Endoplasmic Reticulum (ER) stress often associated to autophagy deregulation. The latter can be induce...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1164-5
更新日期:2019-04-12 00:00:00
abstract:BACKGROUND:The aim of this retrospective study was to assess the results concerning the regional and systemic toxicity and complications in 242 chemo-hyperthermal treatments (HILPs) for lower limb melanoma. PATIENTS AND METHODS:60 HILPs (G-A) were performed with mild HT plus L-PAM (10 mg/lt) +/- D-actimomycin; 74 HILP...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-27-67
更新日期:2008-11-12 00:00:00
abstract:BACKGROUND:In response to diverse genotoxic stimuli p53 is activated as transcription factor to exert its tumor-suppressor function. P53 activation requires protein stabilization, nuclear localization and posttranslational modifications in key residues that may influence p53 selection of target genes. Among them, serin...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-014-0079-4
更新日期:2014-09-27 00:00:00
abstract::Glioblastoma multiform (GBM) is the most common tumour of the central nervous system in humans. Unfortunately its prognosis is poor and because of the lack of efficacious therapies, immunotherapy is a potential treatment. Transfer factors (TF) are low molecular weight dialysable products extracted from immune cells wh...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND:Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1), a long noncoding RNA, is significantly highly expressed and associated with metastasis and poor prognosis in many cancers, including nasopharyngeal carcinoma (NPC). In this study, we aim to identify the role of AFAP1-AS1 acting as an oncogenic ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0918-9
更新日期:2018-10-16 00:00:00
abstract:BACKGROUND:Glioma is the most common intracranial neoplasm with vasculogenic mimicry formation as one form of blood supply. Many RNA-binding proteins and long non-coding RNAs are involved in tumorigenesis of glioma. METHODS:The expression of ZRANB2, SNHG20 and FOXK1 in glioma were detected by real-time PCR or western ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1073-7
更新日期:2019-02-11 00:00:00
abstract::Tumours involving the scrotum are rare and primary malignant melanoma is among the rarest of these lesions. Between 1949 and 1996 only 7 cases have been reported. We present two cases of scrotal melanoma. The current recommendations and management strategies are discussed on the basis of a review of the literature. ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:
更新日期:1998-03-01 00:00:00
abstract::Since the social and financial impact of AML therapy is becoming more and more relevant we analyzed the cost of induction therapy of two different regimens. The first one is part of the widely employed EORTC-GIMEMA AML-10 and consists often days of therapy. The second (FLANG) is a short (three day), Fludarabine, Ara-C...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2001-06-01 00:00:00
abstract::The present study assesses the adaptation of a group of female patients with either manifest or suspected breast cancer who have undergone Magnetic Resonance Imaging (MRI) after receiving psychological support. Several studies in literature have reported the effectiveness of such support in reducing anti-oxidant and d...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2006-12-01 00:00:00