Wilms’ tumor gene 1 (WT1) plays complex roles in tumorigenesis, acting as tumorsuppressor gene or an oncogene depending on the cellular context. WT1expression has been variably reported in both benign and malignant peripheralnerve sheath tumors (MPNSTs) by means of immunohistochemistry. The aim of thepresent study was to characterize its potential pathogenetic role in these relativelyuncommon malignant tumors. Firstly, immunohistochemical analyses in MPNSTsNF96.2 cell line showed strong WT1 staining in nuclear and perinuclear areas ofneoplastic cells. Thus, we investigated the effects of silencing WT1 by RNAinterference. Through Western Blot analysis and proliferation assay we found thatWT1 knockdown leads to the reduction of cell growth in a time- and dosedependentmanner. siWT1 inhibited proliferation of sNF96.2 cell lines likely byinfluencing cell cycle progression through a decrease in the protein levels of cyclinD1 and inhibition of Akt phosphorylation compared to the control cells. Theseresults indicate that WT1 knockdown attenuates the biological behavior of MPNSTcells by decreasing Akt activity, demonstrating that WT1 is involved in thedevelopment and progression of MPNSTs. Thus, WT1 is suggested to serve as apotential therapeutic target for MPNSTs.
Wilms’ Tumor Gene 1 (WT1) silencing inhibits proliferation of malignant peripheral nerve sheath tumor sNF96.2 cell line.
PARENTI, Rosalba;CARDILE, Venera;GRAZIANO, ADRIANA CAROL;PARENTI, Carmela;LO FURNO, DEBORA;MAGRO, Gaetano Giuseppe
2014-01-01
Abstract
Wilms’ tumor gene 1 (WT1) plays complex roles in tumorigenesis, acting as tumorsuppressor gene or an oncogene depending on the cellular context. WT1expression has been variably reported in both benign and malignant peripheralnerve sheath tumors (MPNSTs) by means of immunohistochemistry. The aim of thepresent study was to characterize its potential pathogenetic role in these relativelyuncommon malignant tumors. Firstly, immunohistochemical analyses in MPNSTsNF96.2 cell line showed strong WT1 staining in nuclear and perinuclear areas ofneoplastic cells. Thus, we investigated the effects of silencing WT1 by RNAinterference. Through Western Blot analysis and proliferation assay we found thatWT1 knockdown leads to the reduction of cell growth in a time- and dosedependentmanner. siWT1 inhibited proliferation of sNF96.2 cell lines likely byinfluencing cell cycle progression through a decrease in the protein levels of cyclinD1 and inhibition of Akt phosphorylation compared to the control cells. Theseresults indicate that WT1 knockdown attenuates the biological behavior of MPNSTcells by decreasing Akt activity, demonstrating that WT1 is involved in thedevelopment and progression of MPNSTs. Thus, WT1 is suggested to serve as apotential therapeutic target for MPNSTs.File | Dimensione | Formato | |
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