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Downregulation and forced expression of EWS-Fli1 fusion gene results in changes in the expression of G(1)regulatory genes.
Br J Cancer. 2001 Mar 23; 84(6):768-75.BJ

Abstract

Chromosomal translocation t(11;22)(q24:q12) is detected in approximately 90% of tumours of the Ewing family (ET). This translocation results in EWS-Fli1 gene fusion which produces a EWS-Fli1 fusion protein acting as an aberrant transcriptional activator. We previously reported that the inhibition of EWS-Fli1 expression caused the G(0)/G(1)arrest of ET cells. We, therefore, hypothesized that EWS-Fli1 may affect the expression of G(1)regulatory genes. Downregulation of EWS-Fli1 fusion proteins was observed 48 hours after the treatment with EWS-Fli1 antisense oligonucleotides. The expressions of G(1)cyclins, cyclin D1 and cyclin E, were markedly decreased in parallel with the reduction of EWS-Fli1 fusion protein. On the other hand, the expression of p21 and p27, which are important cyclin-dependent kinase inhibitors (CKIs) for G(1)--S transition, was dramatically increased after the treatment with EWS-Fli1 antisense oligonucleotides. RT-PCR analysis showed that alteration of the expressions of the cyclins and CKIs occurred at the mRNA level. Furthermore, transfection of EWS-Fli1 cDNA to NIH3T3 caused transformation of the cells and induction of the expression of cyclin D1 and E. Clinical samples of ET also showed a high level of expression of cyclin D1 mRNA, whereas mRNAs for p21 and p27 were not detected in the samples. These findings strongly suggest that the G(1)--S regulatory genes may be involved in downstream of EWS-Fli1 transcription factor, and that the unbalanced expression of G(1)--S regulatory factors caused by EWS-Fli1 may lead to the tumorigenesis of ET.

Authors+Show Affiliations

Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11259090

Citation

Matsumoto, Y, et al. "Downregulation and Forced Expression of EWS-Fli1 Fusion Gene Results in Changes in the Expression of G(1)regulatory Genes." British Journal of Cancer, vol. 84, no. 6, 2001, pp. 768-75.
Matsumoto Y, Tanaka K, Nakatani F, et al. Downregulation and forced expression of EWS-Fli1 fusion gene results in changes in the expression of G(1)regulatory genes. Br J Cancer. 2001;84(6):768-75.
Matsumoto, Y., Tanaka, K., Nakatani, F., Matsunobu, T., Matsuda, S., & Iwamoto, Y. (2001). Downregulation and forced expression of EWS-Fli1 fusion gene results in changes in the expression of G(1)regulatory genes. British Journal of Cancer, 84(6), 768-75.
Matsumoto Y, et al. Downregulation and Forced Expression of EWS-Fli1 Fusion Gene Results in Changes in the Expression of G(1)regulatory Genes. Br J Cancer. 2001 Mar 23;84(6):768-75. PubMed PMID: 11259090.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Downregulation and forced expression of EWS-Fli1 fusion gene results in changes in the expression of G(1)regulatory genes. AU - Matsumoto,Y, AU - Tanaka,K, AU - Nakatani,F, AU - Matsunobu,T, AU - Matsuda,S, AU - Iwamoto,Y, PY - 2001/3/22/pubmed PY - 2001/5/5/medline PY - 2001/3/22/entrez SP - 768 EP - 75 JF - British journal of cancer JO - Br J Cancer VL - 84 IS - 6 N2 - Chromosomal translocation t(11;22)(q24:q12) is detected in approximately 90% of tumours of the Ewing family (ET). This translocation results in EWS-Fli1 gene fusion which produces a EWS-Fli1 fusion protein acting as an aberrant transcriptional activator. We previously reported that the inhibition of EWS-Fli1 expression caused the G(0)/G(1)arrest of ET cells. We, therefore, hypothesized that EWS-Fli1 may affect the expression of G(1)regulatory genes. Downregulation of EWS-Fli1 fusion proteins was observed 48 hours after the treatment with EWS-Fli1 antisense oligonucleotides. The expressions of G(1)cyclins, cyclin D1 and cyclin E, were markedly decreased in parallel with the reduction of EWS-Fli1 fusion protein. On the other hand, the expression of p21 and p27, which are important cyclin-dependent kinase inhibitors (CKIs) for G(1)--S transition, was dramatically increased after the treatment with EWS-Fli1 antisense oligonucleotides. RT-PCR analysis showed that alteration of the expressions of the cyclins and CKIs occurred at the mRNA level. Furthermore, transfection of EWS-Fli1 cDNA to NIH3T3 caused transformation of the cells and induction of the expression of cyclin D1 and E. Clinical samples of ET also showed a high level of expression of cyclin D1 mRNA, whereas mRNAs for p21 and p27 were not detected in the samples. These findings strongly suggest that the G(1)--S regulatory genes may be involved in downstream of EWS-Fli1 transcription factor, and that the unbalanced expression of G(1)--S regulatory factors caused by EWS-Fli1 may lead to the tumorigenesis of ET. SN - 0007-0920 UR - https://www.unboundmedicine.com/medline/citation/11259090/Downregulation_and_forced_expression_of_EWS_Fli1_fusion_gene_results_in_changes_in_the_expression_of_G_1_regulatory_genes_ L2 - https://doi.org/10.1054/bjoc.2000.1652 DB - PRIME DP - Unbound Medicine ER -