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Epstein‐Barr virus antagonizes the antiproliferative activity of transforming growth factor‐β but does not abolish its signaling
Author(s) -
Horndasch Manuela,
Raschke Eva E.,
Bommer Guido,
Schuhmacher Marino,
Dumont Elisabeth,
KuklikRoos Conny,
Eick Dirk,
Kempkes Bettina
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10626
Subject(s) - transforming growth factor , epstein–barr virus , cell culture , biology , microbiology and biotechnology , signal transduction , cell growth , transforming growth factor beta , apoptosis , cancer research , virus , immunology , genetics
TGF‐β induces apoptosis and inhibits the proliferation of EBV‐negative B‐lymphoma cell lines. In contrast, EBV‐immortalized B cells are resistant to both the proapoptotic and the antiproliferative activities of TGF‐β. We have generated a lymphoblastoid cell line, in which we can switch on and off the EBV‐specific transcriptional program driven by EBNA2. When these cells express the EBNA2‐driven phenotype, they are resistant to TGF‐β‐mediated growth arrest. We used this cell line to readdress the question of how EBV can overcome the antiproliferative TGF‐β activity. We show here that EBV‐driven cells remain TGF‐β‐responsive since TGF‐β target genes are readily induced. Thus, EBV can overcome TGF‐β‐mediated growth arrest without interfering with the core machinery of the TGF‐β signaling pathway, which links ligand binding to the induction of TGF‐β target genes. © 2002 Wiley‐Liss, Inc.