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Extinction of tumor antigen expression by SF2/ASF in JCV-transformed cells

Uleri, Elena and Beltrami, Sarah and Gordon, Jennifer and Dolei, Antonina and Kudret Sariyer, Ilker (2011) Extinction of tumor antigen expression by SF2/ASF in JCV-transformed cells. Genes & Cancer, Vol. 2 (7), p. 728-736. eISSN 1947-6027. Article.

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DOI: 10.1177/1947601911424578

Abstract

The human neurotropic polyomavirus JC (JCV) induces a broad range of neural-origin tumors in experimental animals and has been repeatedly detected in several human cancers, most notably neural crest–origin tumors including medulloblastomas and glioblastomas. The oncogenic activity of JCV is attributed to the viral early gene products, large T and small t antigens, as evident by results from in vitro cell culture and in vivo animal studies. Recently, we have shown that alternative splicing factor, SF2/ASF, has the capacity to exert a negative effect on transcription and splicing of JCV genes in glial cells through direct association with a specific DNA motif within the viral promoter region. Here, we demonstrate that SF2/ASF suppresses large T antigen expression in JCV-transformed tumor cell lines, and the expression of SF2/ASF in such tumor cells thereby inhibits the transforming capacity of the viral tumor antigens. Moreover, down-regulation of SF2/ASF in viral-transformed tumor cell lines induces growth and proliferation of the tumor cells. Mapping analysis of the minimal peptide domain of SF2/ASF responsible for JCV promoter silencing and tumor suppressor activity suggests that amino acid residues 76 to 100 of SF2/ASF are functionally sufficient to suppress the growth of the tumor cells. These observations demonstrate a role for SF2/ASF in JCV-mediated cellular transformation and provide a new avenue of research to pathogenic mechanisms of JCV-induced tumors.

Item Type:Article
ID Code:8547
Status:Published
Refereed:Yes
Uncontrolled Keywords:SF2/ASF, JC virus, transcription, tumor antigen
Subjects:Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:Sage
eISSN:1947-6027
Copyright Holders:© The Author(s) 2011
Deposited On:25 Jan 2013 09:18

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