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EWS-WT1 Chimeric Protein in Desmoplastic Small Round Cell Tumor is a Potent Transactivator of FGFR4 | OMICS International | Abstract
ISSN: 1948-5956

Journal of Cancer Science & Therapy
Open Access

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Research Article

EWS-WT1 Chimeric Protein in Desmoplastic Small Round Cell Tumor is a Potent Transactivator of FGFR4

Tsuyoshi Saito1*, Mayumi Yokotsuka2, Toru Motoi3, Hiroshi Iwasaki4, Toshitaka Nagao2, Marc Ladanyi5 and Takashi Yao1

1Department of Human Pathology, Juntendo University, School of Medicine, Tokyo, Japan

2Department of Human Pathology, Tokyo Medical University, Tokyo, Japan

3Department of Pathology, Komagome Hospital, Tokyo, Japan

4Department of Pathology, School of Medicine, Fukuoka University, Japan

5Department of Pathology, Memorial Sloan-Kettering Cancer Center, NY, USA

*Corresponding Author:
Tsuyoshi Saito, M.D, Ph.D
Department of Human Pathology
Juntendo University
School of Medicine
Hongo 2-1-1, Bunkyo-ku
Tokyo, Japan 113-8421
E-mail: [email protected]

Received date: August 26, 2012; Accepted date: September 22, 2012; Published date: September 24, 2012

Citation: Saito T, Yokotsuka M, Motoi T, Iwasaki H, Nagao T, et al. (2012) EWSWT1 Chimeric Protein in Desmoplastic Small Round Cell Tumor is a Potent Transactivator of FGFR4. J Cancer Sci Ther 4: 335-340. doi: 10.4172/1948-5956.1000164

Copyright: © 2012 Saito T, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited


Desmoplastic small round cell tumor (DSRCT) is a rare but highly aggressive malignant neoplasm that typically involves the abdominal or pelvic peritoneum in children and young adults. This tumor is characterized by the presence of a specific EWS-WT1 fusion gene, which is the result of recurrent chromosomal translocation, t(11;22)(p13;q12). EWS encodes a putative RNA binding protein of unknown function with an N-terminal domain that mediates potent transcriptional activation when fused to heterologous DNA binding domains. WT1 is a tumor suppressor gene initially identified based on its inactivation in Wilms tumor. The chimeric proteins resulting from these chromosomal translocations usually possess gain-of-function transcriptional activities and define histologically and biologically distinct tumor types. EWS-WT1 has two isoforms of EWS-WT1(-KTS) and EWS-WT1(+KTS). Previous studies have identified several EWS-WT1(-KTS) target genes, most of which are involved in growth factor signaling. In the current study, using an exogenous EWS-WT1(-KTS) induction system along with the selection from candidates for target genes based on the microarray data, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential EWS-WT1(-KTS) target and this induction accompanied with increased phosphorylation form of Akt and MAPK, suggesting a post-transcriptional modulation by EWS-WT1(-KTS). In addition, CTNNB1 was also identified as a potential EWS-WT1(-KTS) target that defines epithelial characteristics of DSRCT. Furthermore, up-regulation of CTNNB1 driven by EWS-WT1(-KTS) was independent of FGFR4 regulation. Expressions of FGFR4 and CTNNB1 in DSRCT clinical samples were confirmed by immunohistochemistry. This study provides regulatory mechanism of FGFR4 in DSRCT and also novel insights into the acquisition of epithelial characteristics in DSRCT.


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