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

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...

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Bibliographic Details
Published in:PloS one 2014-12, Vol.9 (12), p.e114333
Main Authors: Parenti, Rosalba, Cardile, Venera, Graziano, Adriana Carol Eleonora, Parenti, Carmela, Venuti, Assunta, Bertuccio, Maria Paola, Furno, Debora Lo, Magro, Gaetano
Format: Article
Language:English
Subjects:
Apoptosis
Biology and Life Sciences
Brain cancer
Cell cycle
Cell growth
Cell Line, Tumor
Cell Proliferation - genetics
Cell Transformation, Neoplastic - genetics
Cyclin D1 - biosynthesis
Cyclin D1 - genetics
Epidermal growth factor
Gene Expression Regulation, Neoplastic - genetics
Genes
Genetic engineering
Humans
Immunohistochemistry
Kinases
Medicine and Health Sciences
Melanoma
Neurilemmoma - genetics
Neurilemmoma - pathology
Pathogenesis
Physiology
RNA Interference
Signal transduction
Therapeutic applications
Tumors
WT1 Proteins - antagonists & inhibitors
WT1 Proteins - genetics
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0114333