To understand the role of p63 in osteosarcoma

Abstract

Osteosarcoma is the most common primary bone malignancy. It is highly heterogenous genetically and aggressive in nature. P63 being a member of the p53 family is implicated in tumorigenesis. Mutations in TP63 genes are rarely found in cancers, but in syndromes with limb abnormalities. Upregulation or downregulation of p63 expression, however, was hypothesized to be associated with tumor progression. P63 proteins have two isoforms (TAp63 and DNp63). Both have been proposed acting as either tumor suppressor or oncogene in functions. Besides, their role in the pathogenesis of osteosarcoma is controversial. In this study, two adult human osteosarcoma samples were primary-cultured to established cell lines of OS1 and OS2. They were characterized by comparing with normal human osteoblasts and two commonly used osteosarcoma cell lines MG63 and SaOS2. Interestingly, quantitative RT-PCR found a gradient of p63 expression level, from highest to lowest, across the cell lines of MG63, OS1, normal osteoblasts, OS2 and SaOS2. MG63 and OS1 belong to a group with upregulated p63 expression; whereas OS2 and SaOS2 belong to that with downregulated p63 expression. TAp63 was the only isoform expressed in these cell lines, independent of the p53 level. The upregulation of p63 was associated with decreased metastatic potentials; whereas downregulation of p63 increased. This was further demonstrated by p63 knock-down. Thus, we propose TAp63 expression level as a prognostic marker for osteosarcoma, i.e. the higher the TAp63 expression level, the better the prognosis. Whenever TAp63 expression is downregulated, more aggressive chemotherapy and vigilant monitoring for metastasis are required.