Abstract:
:The transcription factor OTX2 has been implicated as an oncogene in medulloblastoma, which is the most common malignant brain tumor in children. It is highly expressed in most medulloblastomas and amplified in a subset of them. To study the role OTX2 has in medulloblastoma we investigated the downstream pathway of OTX2. We generated D425 medulloblastoma cells in which endogenous OTX2 can be silenced by inducible shRNA. Silencing of OTX2 strongly inhibited cell proliferation and resulted in a neuronal-like differentiation. Expression profiling of time courses after silencing showed a progressive change in gene expression for many cellular processes. Downregulated genes were highly enriched for cell cycle and visual perception genes, while upregulated genes were enriched for genes involved in development and differentiation. This shift is reminiscent of expression changes described during normal cerebellum development where proliferating granule progenitor cells have high OTX2 expression, which diminishes when these cells exit the cell cycle and start to differentiate. ChIP-on-chip analyses of OTX2 in D425 cells identified cell cycle and perception genes as direct OTX2 targets, while regulation of most differentiation genes appeared to be indirect. The expression of many directly regulated genes correlated to OTX2 expression in primary tumors, suggesting the in vivo relevance of these genes and their potential as targets for therapeutic intervention. These analyses provide more insight in the molecular network of OTX2, demonstrating that OTX2 is essential in medulloblastoma and directly drives proliferation by regulation of cell cycle genes.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Bunt J,Hasselt NE,Zwijnenburg DA,Hamdi M,Koster J,Versteeg R,Kool Mdoi
10.1002/ijc.26474subject
Has Abstractpub_date
2012-07-15 00:00:00pages
E21-32issue
2eissn
0020-7136issn
1097-0215journal_volume
131pub_type
杂志文章abstract::Nitrogen-containing bisphosphonates (N-BPs) are effective antiosteolytic agents in patients with multiple myeloma. Preclinical studies have also demonstrated that these agents have direct antitumor effects in vitro and can reduce tumor burden in a variety of animal models, although it is not clear whether such effects...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24758
更新日期:2010-01-01 00:00:00
abstract::Akt is a promising therapeutic target for cancer treatment. In our study, we have identified that 7-deoxynarciclasine (7-DONCS) is a potential inhibitor of Akt, which results in the repression of multiple oncogenic processes in hepatocellular carcinoma (HCC). We have found that 7-DONCS suppresses the growth of HCC by ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32395
更新日期:2019-12-15 00:00:00
abstract::The recently identified cell adhesion regulator (CAR) modulates the process of integrin-mediated cell adhesion. The CAR gene is located on 16q, a locus at which high levels of allelic losses have been demonstrated in advanced human hepatocellular carcinoma (HCC). We studied the possible involvement of the CAR gene in ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970620)74:3<251::aid-ijc
更新日期:1997-06-20 00:00:00
abstract::An important feature of cytochrome P450 (CYP) 2B1 is its high ability to convert the prodrug cyclophosphamide (CPA) to therapeutically cytotoxic metabolites, resulting in interstrand DNA-cross-linking and cell death. We have examined whether and how the phosphorylation of CYP2B1 influences CPA metabolic activation in ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.1517
更新日期:2001-12-01 00:00:00
abstract::Cancer stem cells (CSCs) are considered as responsible for initiation, maintenance and recurrence of solid tumors, thus representing the key for tumor eradication. The antitumor activity of extracellular vesicles (EVs) derived from different stem cell sources has been investigated with conflicting results. In our stud...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32925
更新日期:2020-09-15 00:00:00
abstract::CXCR1 and CXCR2 are receptors for CXCL-8 and are differentially expressed on melanoma and endothelial cells. In this study, we determined the functional role of these receptors in melanoma progression. We stably knock-down the expression of CXCR1 and/or CXCR2 in A375-SM (SM; high metastatic) human melanoma cells by sh...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24714
更新日期:2010-01-15 00:00:00
abstract::Previous literature, although not consistent, suggests that moderate alcohol consumption might be associated with decreased risk of renal cell carcinoma (RCC) in women. Thus, we examined the association between alcohol intake and the incidence of RCC by analyzing data from the Swedish Mammography Cohort, a population-...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.21231
更新日期:2005-12-10 00:00:00
abstract::It has become axiomatic that critical windows of susceptibility to genotoxins exist and that genetic damage in utero may be a trigger for later life cancers. Data supporting this critical window hypothesis are remarkably few. This study provides a quantitative bridge between DNA damage by the liver carcinogen aflatoxi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29102
更新日期:2015-03-15 00:00:00
abstract::We have examined the effect of various cell monolayers on the ability of mouse spleen cells to lyse tumor cell targets (natural cytotoxicity reaction). Natural killer (NK) cell activity was reduced by as much as 75% depending on the cell substrate, with the greatest protection afforded by endothelial cells. Cell adhes...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910410612
更新日期:1988-06-15 00:00:00
abstract::The expression of fibronectin (FN) isoforms containing the extradomains A and B (ED-A+ and ED-B+ FNs) as well as a differentially O-glycosylated oncofetal form of the protein (onf-FN) was investigated in 6 normal human anterior pituitaries and 25 human pituitary adenomas. In normal tissue, immunohistochemical experime...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910610106
更新日期:1995-03-29 00:00:00
abstract::Epidemiologic evidence on the association of antioxidant intake and prostate cancer incidence is inconsistent. Total antioxidant intake and prostate cancer incidence have not previously been examined. Using the ferric-reducing antioxidant potential (FRAP) assay, the total antioxidant content (TAC) of diet and suppleme...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.28438
更新日期:2014-03-01 00:00:00
abstract::We examined cancer-associated fibroblasts (CAFs) and a panel of immunohistochemical markers of epithelial-mesenchymal transition (EMT) in 19 pair-matched oral tongue squamous cell carcinoma (SCC) and metastatic tumors to regional lymph nodes (RLNs). alpha-Smooth muscle actin (alpha-SMA) was studied to identify CAFs. E...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.25358
更新日期:2010-09-01 00:00:00
abstract::The p53 tumor suppressor pathway is impaired in more than 90% of cervical cancers and cancer-derived cell lines as a result of infection by human papillomavirus (HPV). The HPV E6 oncoprotein forms complexes with p53 and promotes its degradation via ubiquitin-dependent mechanism. In our study, we attempted to improve t...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.26013
更新日期:2012-01-15 00:00:00
abstract::Cutaneous T-Cell lymphoma (CTCL) is a non-Hodgkin's lymphoma of unknown pathogenesis. Mycosis fungoides (MF) is a clinically determined subset of CTCL with intensive infiltration of lymphoma cells into the epidermis. To determine whether Epstein-Barr virus (EBV) is associated with these lymphoma cells, we performed mR...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/1097-0215(200102)9999:9999<::aid-ijc1172>3
更新日期:2001-04-15 00:00:00
abstract::The androgen receptor (AR) gene is a transcription factor responsible for mediating the physiological effects of androgens. Evidence suggests that androgens and the androgen receptor are involved in uterine cell proliferation. A polymorphic CAG repeat in exon 1 of the AR gene encodes a polyglutamine tract that is inve...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.21436
更新日期:2006-03-01 00:00:00
abstract::To evaluate the role of chromosome 13 deletions in oral squamous cell carcinoma (SCC) progression and to define the precise localization of putative tumor suppressor genes, we studied tumors from 34 unrelated patients with oral SCC by the polymerase chain reaction (PCR)-loss of heterozygosity (LOH) assay, using 18 dif...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19980821)79:4<312::aid-ijc
更新日期:1998-08-21 00:00:00
abstract::Dimethylarsinic acid (DMA) is a major metabolite of inorganic arsenicals, which are epidemiologically significant chemicals in relation to liver cancer in mammals. The present study was conducted to determine the promoting effects of organic arsenicals related to DMA [monomethylarsonic acid (MMA) and trimethylarsine o...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10471
更新日期:2002-07-10 00:00:00
abstract::In ovarian cancer cells, the macrophage colony-stimulating factor-1 (CSF-1) induces the release of plasminogen activator inhibitor-2 (PAI-2), and high levels of PAI-2 as well as of CSF-1 in ovarian cancer ascites are independently correlated with poor outcome. We now study the effect of CSF-1 on PAI-2 expression in vi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19971219)74:6<571::aid-ijc
更新日期:1997-12-19 00:00:00
abstract::The Ontario Cancer Registry (OCR) and the Surveillance, Epidemiology and End Results (SEER) databases were used to describe temporal trends in the incidence and survival of squamous cancers of the upper aerodigestive tract (UADT) in Ontario and the US between 1984 and 2001. Between the 1984-86 and 1999-01 periods, the...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24533
更新日期:2009-11-01 00:00:00
abstract::Breast cancer is heterogeneous in clinical behavior by subtypes; however, it is unclear how this heterogeneity is related to epidemiological factors. To evaluate the differences in epidemiological factors by breast tumor subtypes, we investigated the associations of epidemiological factors between tumor subtypes in Ko...
journal_title:International journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1002/ijc.28685
更新日期:2014-08-01 00:00:00
abstract::Lymphatic leukemia developed in C57BL/6 mice following inoculation of normal thymocytes that and been co-cultured on leukemic thymus epithelial reticulum monolayer cells. Using thymocytes genetically marked in Ly membrane antigens, we showed that the thymomas which developed were produced by the co-cultured thymocytes...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910210119
更新日期:1978-01-15 00:00:00
abstract::A population-based case-control study was conducted to examine the effect of ingestion of vitamin C, carotenoids and retinol on risk of pharyngeal cancer. Data were available from 166 cases of pharyngeal cancer or their next-of-kin, and from 547 controls similar in age and sex to the cases. Odds ratios (ORs) relating ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910440406
更新日期:1989-10-15 00:00:00
abstract::We describe a new, spontaneously occurring BALB/c-derived murine T-cell leukemia. The leukemic cells, designated LB, grow rapidly and progressively in the syngeneic host with no signs of effective immunological resistance. LB cells expressed the Thy-1+, Lyt-2+, L3T4-, CD3- class-I+, CD25+ (IL-2 receptor, IL-2R), class...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910450129
更新日期:1990-01-15 00:00:00
abstract::Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Little is known about its molecular pathogenesis and the relevance of DNA methylation for disease initiation and progression. Nevertheless, promoter methylation of some genes has been implicated as potential marker for HCC. Thirty-four HCC, 34...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23433
更新日期:2008-06-15 00:00:00
abstract::The EWS/Fli-1 fusion gene, a product of the translocation t(11;22, q24;q12), is detected in 85% of Ewing sarcomas and primitive neuroectodermal tumors. It is thought to be a transcriptional activator that plays a significant role in tumorigenesis. In this study, we developed a novel EWS/Fli-1 blockade system using RNA...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.25564
更新日期:2011-01-01 00:00:00
abstract::Morphologic and metabolic studies have been carried out on Friend leukemia cell (FLC) tumors (grown in DBA/2 mice) or fibrosarcomas (grown in C3H/HeN or C3H/HeJ mice) shortly after peritumoral injection of recombinant mouse tumor necrosis factor (TNF) alpha. Marked vascular congestion and focal extravasation of erythr...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910420420
更新日期:1988-10-15 00:00:00
abstract::More women are surviving after breast cancer due to early detection and modern treatment strategies. Body weight also influences survival. We aimed to characterize associations between postdiagnosis weight change and prognosis in postmenopausal long-term breast cancer survivors. We used data from a prospective populat...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.33181
更新日期:2021-01-01 00:00:00
abstract::Tumor growth and metastasis of lacZ-transduced murine lymphoma ESbL cells inoculated into syngeneic DBA/2 mice are characterized by a transient plateau phase with a constant tumor diameter and low metastatic load, indicating a host response against the tumor. Here we show that endothelial cells participate in a T-cell...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910630318
更新日期:1995-11-03 00:00:00
abstract::Seven human ocular melanoma cell lines were established in vitro and 3 of these, GU-4, LLN-40 and its subline C17-11, were characterized. Mice were immunized with these ocular melanoma cell lines, and 2 hybridomas producing monoclonal IgG1 antibodies (MAb) were produced. MAb 2/10SN recognizes a 44-kDa monomeric protei...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910510510
更新日期:1992-07-09 00:00:00
abstract::Bcl-2 expression is up-regulated in prostate cancer cells after androgen ablation and associated with development of androgen independence and chemoresistance. We recently reported that antisense Bcl-2 oligodeoxynucleotides (ODNs) delay progression to androgen independence in the androgen-dependent (AD) human LNCaP pr...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/1097-0215(200002)9999:9999<::aid-ijc1131>3
更新日期:2001-03-15 00:00:00