Details

Autor(en) / Beteiligte

• Parenti, Rosalba
• Cardile, Venera
• Graziano, Adriana Carol Eleonora
• Parenti, Carmela
• Venuti, Assunta
• Bertuccio, Maria Paola
• Furno, Debora Lo
• Magro, Gaetano
• Brown, Keith William

Titel

Wilms' tumor gene 1 (WT1) silencing inhibits proliferation of malignant peripheral nerve sheath tumor sNF96.2 cell line

Ist Teil von

• PloS one, 2014-12, Vol.9 (12), p.e114333

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2014

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Wilms' tumor gene 1 (WT1) plays complex roles in tumorigenesis, acting as tumor suppressor gene or an oncogene depending on the cellular context. WT1 expression has been variably reported in both benign and malignant peripheral nerve sheath tumors (MPNSTs) by means of immunohistochemistry. The aim of the present study was to characterize its potential pathogenetic role in these relatively uncommon malignant tumors. Firstly, immunohistochemical analyses in MPNST sNF96.2 cell line showed strong WT1 staining in nuclear and perinuclear areas of neoplastic cells. Thus, we investigated the effects of silencing WT1 by RNA interference. Through Western Blot analysis and proliferation assay we found that WT1 knockdown leads to the reduction of cell growth in a time- and dose-dependent manner. siWT1 inhibited proliferation of sNF96.2 cell lines likely by influencing cell cycle progression through a decrease in the protein levels of cyclin D1 and inhibition of Akt phosphorylation compared to the control cells. These results indicate that WT1 knockdown attenuates the biological behavior of MPNST cells by decreasing Akt activity, demonstrating that WT1 is involved in the development and progression of MPNSTs. Thus, WT1 is suggested to serve as a potential therapeutic target for MPNSTs.