Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice

Pérez–Mancera, Pedro A.; Pérez-Losada, Jesús; Sánchez-Martı́n, Manuel; Rodríguez-García, M A; Flores, Teresa; Battaner, E.; Gutiérrez‐Adán, Alfonso; Pintado, B.; Sánchez-Garcı́a, Isidro

doi:10.1038/sj.onc.1205220

Cited by 26 publications

(21 citation statements)

References 22 publications

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“…White adipose tissue from Ef1a-FUS or Ef1a-CHOP single transgenic mice was normal. Creation of double transgenic Ef1a-FUS ϫ Ef1a-CHOP mice resulted in liposarcomas that develop at the same rate as the FUS-CHOP fusion gene mice (Perez-Mancera et al, 2002). Tumors were not identified in any other tissues, despite the ubiquitous expression from the Ef1a promoter.…”

Section: Myxoid Liposarcomamentioning

confidence: 91%

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Animal models of soft-tissue sarcoma

Dodd

Mito

Kirsch

2010

Disease Models &Amp; Mechanisms

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Soft-tissue sarcomas (STSs) are rare mesenchymal tumors that arise from muscle, fat and connective tissue. Currently, over 75 subtypes of STS are recognized. The rarity and heterogeneity of patient samples complicate clinical investigations into sarcoma biology. Model organisms might provide traction to our understanding and treatment of the disease. Over the past 10 years, many successful animal models of STS have been developed, primarily genetically engineered mice and zebrafish. These models are useful for studying the relevant oncogenes, signaling pathways and other cell changes involved in generating STSs. Recently, these model systems have become preclinical platforms in which to evaluate new drugs and treatment regimens. Thus, animal models are useful surrogates for understanding STS disease susceptibility and pathogenesis as well as for testing potential therapeutic strategies.

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Section: Myxoid Liposarcomamentioning

confidence: 91%

“…To determine the protein domain that is sufficient for tumorigenesis, the FUS and CHOP genes were examined in separate mouse models (Perez-Mancera et al, 2002). White adipose tissue from Ef1a-FUS or Ef1a-CHOP single transgenic mice was normal.…”

Section: Myxoid Liposarcomamentioning

confidence: 99%

Animal models of soft-tissue sarcoma

Dodd

Mito

Kirsch

2010

Disease Models &Amp; Mechanisms

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“…No studies have analyzed FUS expression in human cancers, including GC. However, it has been shown that expression of the FUS domain restores liposarcoma development in CHOP-transgenic mice (40), suggesting that gain-offunction mutation of both FUS and CHOP is important. In the present study, FUS was a candidate marker for tumor progression, and we showed that a high level of FUS expression was associated with advanced N grade and stage.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profile of Gastric Carcinoma

et al. 2004

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Gastric carcinoma (GC) is one of the most common malignancies worldwide. To better understand the genetic basis of this disease, we performed serial analysis of gene expression (SAGE) on four primary GC samples and one associated lymph node metastasis. We obtained a total of 137,706 expressed tags (Gene Expression Omnibus accession number GSE 545, SAGE Hiroshima gastric cancer tissue), including 38,903 that were unique. Comparing tags from our GC libraries containing different stages and different histologies, we found several genes and tags that are potentially involved in invasion, metastasis, and carcinogenesis. Among these, we selected 27 genes and measured mRNA expression levels in an additional 46 GC samples by quantitative reverse transcription-PCR. Frequently overexpressed genes (tumor/normal ratio > 2) were COL1A1 (percentage of cases with overexpression, 78.3%), CDH17 (73.9%), APOC1 (67.4%), COL1A2 (58.7%), YF13H12 (52.2%), CEACAM6 (50.0%), APOE (50.0%), REGIV (47.8%), S100A11 (41.3%), and FUS (41.3%). Among these genes, mRNA expression levels of CDH17 and APOE were associated with depth of tumor invasion (P ‫؍‬ 0.0060 and P ‫؍‬ 0.0139, respectively), and those of FUS and APOE were associated with degree of lymph node metastasis (P ‫؍‬ 0.0416 and P ‫؍‬ 0.0006, respectively). In addition, mRNA expression levels of FUS, COL1A1, COL1A2, and APOE were associated with stage (P ‫؍‬ 0.0414, P ‫؍‬ 0.0156, P ‫؍‬ 0.0395, and P ‫؍‬ 0.0125, respectively). Quantitative reverse transcription-PCR analysis also showed a high level of REGIV expression (>100 arbitrary units) in 14 of 46 GC samples (30.4%) but not in noncancerous tissues. We detected V5-tagged RegIV protein in the culture media of cells transfected with pcDNA-RegIV-V5 by Western blot. Our results provide a list of candidate genes that are potentially involved in invasion, metastasis, and carcinogenesis of GC. REGIV may serve as a specific biomarker for GC.

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“…Thus, transgenic mice expressing FUS-CHOP or CHOP-FUS transgenes under the control of the ubiquitous E1Fa promoter gave rise to similar liposarcomas that resemble their human counterparts [66,67]. On the other hand, although the uncontrolled expression of CHOP after the chromosomal translocation seems to play a leading role in liposarcoma development [64], transgenic mice expressing CHOP alone do not develop any tumor [67] and the expression of FUS restores liposarcoma development in these CHOP-transgenic mice [68]. These results provide evidence that the FUS portion of FUS-CHOP also plays a specific and critical role in the pathogenesis of liposarcoma.…”

Section: Human Mscsmentioning

confidence: 99%

Modeling sarcomagenesis using multipotent mesenchymal stem cells

2011

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Because of their unique properties, multipotent mesenchymal stem cells (MSCs) represent one of the most promising adult stem cells being used worldwide in a wide array of clinical applications. Overall, compelling evidence supports the long-term safety of ex vivo expanded human MSCs, which do not seem to transform spontaneously. However, experimental data reveal a link between MSCs and cancer, and MSCs have been reported to inhibit or promote tumor growth depending on yet undefined conditions. Interestingly, solid evidence based on transgenic mice and genetic intervention of MSCs has placed these cells as the most likely cell of origin for certain sarcomas. This research area is being increasingly explored to develop accurate MSC-based models of sarcomagenesis, which will be undoubtedly valuable in providing a better understanding about the etiology and pathogenesis of mesenchymal cancer, eventually leading to the development of more specific therapies directed against the sarcoma-initiating cell. Unfortunately, still little is known about the mechanisms underlying MSC transformation and further studies are required to develop bona fide sarcoma models based on human MSCs. Here, we comprehensively review the existing MSC-based models of sarcoma and discuss the most common mechanisms leading to tumoral transformation of MSCs and sarcomagenesis.

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Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice

Cited by 26 publications

References 22 publications

Animal models of soft-tissue sarcoma

Animal models of soft-tissue sarcoma

Gene Expression Profile of Gastric Carcinoma

Modeling sarcomagenesis using multipotent mesenchymal stem cells

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