Abstract:
BACKGROUND:Human placental development resembles tumorigenesis, due to the invasive and fusogenic potential of trophoblasts. However, these features are tightly controlled in trophoblasts. Disturbance of this spatial and temporal regulation is thought to contribute to the rare formation of choriocarcinomas. Promoter hypermethylation and loss of the tumor suppressor Retinoic acid receptor responder 1 (RARRES1) were shown to contribute to cancer progression. Our study investigated the epigenetic and transcriptional regulation of RARRES1 in healthy human placenta in comparison to choriocarcinoma cell lines and cases. METHODS:Three choriocarcinoma cell lines (Jeg-3, JAR and BeWo) were treated with three different retinoic acid derivates (Am580, Tazarotene and all-trans retinoic acid) and 5-aza-2'-deoxycytidine. We analyzed RARRES1 promoter methylation by pyrosequencing and performed realtime-PCR quantification to determine RARRES1 expression in placental tissue and trophoblastic cell lines. Additionally, RARRES1 was stained in healthy placentas and in biopsies of choriocarcinoma cases (n = 10) as well as the first trimester trophoblast cell line Swan71 by immunofluorescence and immunohistochemistry. RESULTS:In the choriocarcinoma cell lines, RARRES1 expression could not be induced by sole retinoic acid treatment. Stimulation with 5-aza-2'-deoxycytidine significantly induced RARRES1 expression, which then could be further increased with Am580, Tazarotene and all-trans retinoic acid. In comparison to healthy placenta, choriocarcinoma cell lines showed a hypermethylation of the RARRES1 promoter, which correlated with a reduced RARRES1 expression. In concordance, RARRES1 protein expression was lost in choriocarcinoma tissue. Additionally, in the trophoblastic cell line Swan71, we found a significant induction of RARRES1 expression with increased cell density, during mitosis and in syncytial knots. CONCLUSIONS:Our findings showed that RARRES1 expression is absent in choriocarcinoma due to promoter methylation. Based on our analysis, we hypothesize that RARRES1 might exert tumor suppressive functions in multiple cellular processes (e.g. cell cycle regulation, adhesion, invasion and apoptosis).
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Huebner H,Strick R,Wachter DL,Kehl S,Strissel PL,Schneider-Stock R,Hartner A,Rascher W,Horn LC,Beckmann MW,Ruebner M,Fahlbusch FBdoi
10.1186/s13046-017-0634-xsubject
Has Abstractpub_date
2017-11-23 00:00:00pages
165issue
1eissn
0392-9078issn
1756-9966pii
10.1186/s13046-017-0634-xjournal_volume
36pub_type
杂志文章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:BACKGROUND:Emerging evidence has shown long noncoding RNAs (lncRNAs) exert important roles in colorectal cancer (CRC) tumorigenesis. However, most lncRNAs involved in this process remain undefined and the underlying molecular mechanisms mediated by lncRNAs are largely unknown. METHODS:An unbiased screening was used to...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0896-y
更新日期:2018-09-10 00:00:00
abstract:BACKGROUND:Epidermal growth factor receptor (EGFR)-activating mutations are major determinants in predicting the tumor response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). Noninvasive test for the detection of EGFR mutations is required, especially in NSCLC patients from whom tissue is not...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,多中心研究
doi:10.1186/1756-9966-32-50
更新日期:2013-08-09 00:00:00
abstract::In the original publication of this manuscript [1], Fig. 1 contained a typographical error ('Metabolic' incorrectly written as 'Metabolig'). ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 已发布勘误
doi:10.1186/s13046-020-1532-1
更新日期:2020-02-24 00:00:00
abstract:BACKGROUND:Epilepsy is a frequent symptom in patients with glioma. Although treatment with antiepileptic drugs is generally effective in controlling seizures, drug-resistant patients are not uncommon. Multidrug resistance proteins (MRPs) and P-gp are over-represented in brain tissue of patients with drug-resistant epil...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0546-9
更新日期:2017-06-06 00:00:00
abstract:BACKGROUND:Glioblastoma multiforme is a CNS cancer characterized by diffuse infiltrative growth, aggressive clinical behavior and very poor prognosis. The state-of-art clinical approach to this disease consists of surgical resection followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide. T...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 社论
doi:10.1186/s13046-020-1534-z
更新日期:2020-01-31 00:00:00
abstract::Our previous studies have demonstrated the significant enzymatic activity of glycogen phosphorylase (GP) in the gastric carcinoma and proliferating cells of particular intestinal metaplasia (IM). This paper reviewed the identification of the GP isoform in the gastrointestinal carcinoma, and the investigation on the ro...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:
更新日期:1999-03-01 00:00:00
abstract::RANKL/RANK/OPG system consists of three essential signaling molecules: i) the receptor activator of nuclear factor (NF)-kB-ligand (RANKL), ii) the receptor activator of NF-kB (RANK), and iii) the soluble decoy receptor osteoprotegerin (OPG). Although this system is critical for the regulation of osteoclast differentia...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-018-1001-2
更新日期:2019-01-08 00:00:00
abstract:BACKGROUND:Localized C3 deposition is a well-known factor of inflammation. However, its role in oncoprogression of gastric cancer (GC) remains obscured. This study aims to explore the prognostic value of C3 deposition and to elucidate the mechanism of C3-related oncoprogression for GC. METHODS:From August to December ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 临床试验,杂志文章
doi:10.1186/s13046-019-1514-3
更新日期:2020-01-13 00:00:00
abstract:BACKGROUND:The recently identified phenomenon of double-stranded RNA (dsRNA)-mediated gene activation (RNAa) has been studied extensively, as it is present in humans, mice, and Caenorhabditis elegans, suggesting that dsRNA-mediated RNAa is an evolutionarily conserved mechanism. Previous studies have shown that dsP21-32...
journal_title:Journal of experimental & clinical cancer research : CR
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doi:10.1186/s13046-016-0423-y
更新日期:2016-09-17 00:00:00
abstract:BACKGROUND:DNA methylation has been widely used in classification, early diagnosis, therapy and prediction of metastasis as well as recurrence of cervical cancer. DNMT methyltransferase 1 (DNMT1), which plays a significant role in maintaining DNA methylation status and regulating the expression of tumor suppressor gene...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-30-98
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abstract::Identifying appropriate preclinical cancer models remains a major challenge in increasing the efficiency of drug development. A potential strategy to improve patient outcomes could be selecting the 'right' treatment in preclinical studies performed in patient-derived xenografts (PDXs) obtained by direct implants of su...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-016-0462-4
更新日期:2016-12-05 00:00:00
abstract:BACKGROUND:Yes-associated protein (YAP), an essential component of Hippo pathway, was identified as an oncoprotein which participated in the progression of various malignancies. However, its role in chronic myeloid leukemia (CML) remains to be further clarified. METHODS:The expression of YAP in CML cells was determine...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0414-z
更新日期:2016-09-06 00:00:00
abstract:BACKGROUND:Ovarian cancer (OC) is the most lethal gynecological malignancy and the second leading cause of cancer-related death in women. Treatment with PARP inhibitors (PARPi), such as Olaparib, has been recently introduced for OC patients, but resistance may occur and underlying mechanisms are still poorly understood...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1490-7
更新日期:2020-01-02 00:00:00
abstract::The recent studies have evaluated the relationship between BRCA1 expression and clinical outcome of chemotherapy (mainly focused on platinum-based and toxal-based treatment) in NSCLC patients, but the results were inconclusive and controversial. Our aim of this study was to evaluate this association by literature base...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,meta分析,评审
doi:10.1186/1756-9966-32-15
更新日期:2013-03-15 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-019-1030-5
更新日期:2019-01-17 00:00:00
abstract:BACKGROUND:The chemokine receptors CXCR4 and CCR7 play an important role in cancer invasion and metastasis. This study investigated the expression of CXCR4, CCR7, CXCL12, CCL21, and EGFR to illustrate the role of these biomarkers in breast cancer metastasis and prognosis. METHODS:The CXCR4, CCR7, CXCL12, CCL21, and EG...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-29-16
更新日期:2010-02-24 00:00:00
abstract::Even though it is well established that oxygen-free radicals are the main mechanism responsible for the cytotoxicity produced during radiotherapy, the role of the human antioxidant defense system in clinical radiation oncology is still to be clarified. Changes in the human plasma total peroxyl radical trapping capacit...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 临床试验,杂志文章
doi:
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1179-y
更新日期:2019-05-16 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1044-z
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0422-z
更新日期:2016-09-26 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2004-12-01 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1112-4
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND:The deubiquitinase USP7 has been identified as an oncogene with key roles in tumorigenesis and therapeutic resistance for a series of cancer types. Recently small molecular inhibitors have been developed to target USP7. However, the anticancer mechanism of USP7 inhibitors is still elusive. METHODS:Cell viab...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1457-8
更新日期:2019-11-15 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0486-9
更新日期:2017-01-10 00:00:00
abstract:BACKGROUND:Poly C Binding Protein 1 (PCBP1) is an RNA-binding protein that binds and regulates translational activity of subsets of cellular mRNAs. Depletion of PCBP1 is implicated in various carcinomas, but the underlying mechanism in tumorigenesis remains elusive. METHODS:We performed a transcriptome-wide screen to ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0840-1
更新日期:2018-08-07 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND:Coiled-Coil Domain Containing 88A (CCDC88A) was identified as a substrate of the serine/threonine kinase Akt that is capable of binding to the actin cytoskeleton. The aim of this study was to investigate the potential role of CCDC88A in the migration and invasiveness of pancreatic ductal adenocarcinoma (PDAC...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0466-0
更新日期:2016-12-05 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
abstract:BACKGROUND:When a patient concomitantly uses two or more drugs, a drug-drug interaction (DDI) can possibly occur, potentially leading to an increased or decreased clinical effect of a given treatment. Cancer patients are at high risk of such interactions because they commonly receive multiple medications. Moreover, mos...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-015-0201-2
更新日期:2015-08-25 00:00:00