Overexpression of the T-Box Transcription Factor TBX3 as an early marker of Sarcomas – Associate Professor Sharon Prince
Associate Professor Sharon Prince
Department of Human Biology, Faculty of Health Sciences, University of Cape Town
Overexpression of the T-Box Transcription Factor TBX3 as an early marker of Sarcomas.
According to the World Health Organisation, the annual number of new cancer cases is likely to increase from 11.3 million in 2007 to 15.5 million in 2030, with 70% of these cases occurring in developing countries. Many cancers can be treated or at least managed effectively if detected early. At a molecular level, the initiation of cancer can be characterised, in part, by deregulation of transcription factors and TBX3 has emerged as an important transcription factor in the genesis of cancer. TBX3 plays a critical role in embryonic development and while mutations resulting in decreased levels of TBX3 lead to Ulnar-Mammary Syndrome, increased levels have been linked to a growing list of epithelial-derived cancers including melanoma, breast, liver, bladder and pancreatic cancers. Research in our laboratory has focused on elucidating the role of TBX3 in cancer formation and we have shown that TBX3 plays a direct role in the oncogenic process and specifically in tumour formation, invasion and metastasis of melanoma and breast cancers. We also have novel evidence linking TBX3 to cancers of mesenchymaI origin. Specifically we have data showing that TBX3 is also overexpressed in a number of fibroblast cell lines that are either only immortalised or transformed as well as chondrosarcoma cells (unpublished data). The observation that TBX3 levels are elevated in fibroblasts that are immortalised but not yet fully transformed suggests that the upregulation of TBX3 may be an early event in the development of fibrosarcomas and possibly other sarcomas. To confirm this and to extend our knowledge of the role of TBX3 in mesenchyme-derived cancers we propose to examine the status of TBX3 mRNA and protein levels in a number of patient derived sarcomas at different stages of tumour progression. Results from this study have important implications for the early diagnosis of mesenchyme-derived cancers which are rare but highly aggressive.