Abstract
Wilms’ tumor gene 1 (WT1) plays complex roles in tumorigenesis, acting as tumor suppressor gene or an oncogene depending on the cellular context. A high WT1 expression level was described in various types of human bone and soft-tissue sarcomas, including osteosarcoma (OS), but its function in carcinogenesis is not yet well understood. This study investigated WT1 both in human OS tissues and in human OS MG-63 cell line in which WT1 gene is up-regulated. The results demonstrated that WT1 is expressed in 50% of human OS cases. WT1-silenced MG-63 cells showed deregulation of proteins of cell cycle and down-regulation of PI3K/AKT pathway. Induction of apoptotic programme was also established by activation of caspase-3 and increase of Bax/Bcl2 ratio and p53 protein. This study provided new findings on role of WT1 and indicated an association between WT1 expression, cell cycle and apoptotic machinery. In conclusion, WT1 acts as a tumour promoter in osteosarcoma and it could be a potential therapeutic target.
Highlights
Osteosarcoma (OS) is a primary malignant cancer of bone affecting predominantly the children and the young [1]
It is almost well known that Wilms’ tumor gene 1 (WT1) is a multi-facets protein, playing opposite roles in the same cell population according to the functional context in which it operates [9, 20]
The complex role played by WT1 is largely linked to diversified WT1 gene encoding profile
Summary
Osteosarcoma (OS) is a primary malignant cancer of bone affecting predominantly the children and the young [1]. While therapy for localised OS at onset is on track, a number of OS cases have been observed to be resistant to currently used therapies, leading to disease recurrence and lung metastases [2, 3]. During the last few years, the molecular analysis provided new information about numerous genes and pathways that were associated with OS and its clinical progression. What is becoming clear is that OS is a contextual attribute of distinct patterns of interactions between multiple genes [4]. The presence of ‘‘metastatic heterogeneity’’ characterizing the wide spectrum of patient survival [2] makes high expectations of identifying new molecular markers for improving OS therapeutical approaches
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