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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The highly homologous T-Box transcription factors, TBX2 and TBX3, have distinct roles in the oncogenic process
Genes and Cancer, Volume 1, No. 3, Year 2010
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Description
The T-box transcription factors TBX2 and TBX3 are overexpressed in several cancers and are able to bypass senescence by repressing ARF and p21WAF1/CIP1/SDII. Although these studies suggest that they may both contribute to the oncogenic process by repressing common targets, whether they have redundant or distinct roles in cancers where they are both overexpressed remains to be elucidated. Importantly, when Tbx2 function is inhibited in melanoma cells lacking Tbx3, the cells senesce, but whether this is possible in melanoma cells overexpressing both proteins is not known. An understanding of this issue may have important implications for the design of an effective pro-senescence therapy. In this study, the authors used a sh-RNA approach to knock down TBX2 and TBX3 individually in 2 human melanoma cell lines that overexpress both these factors and then examined their specific involvement in the oncogenic process. They demonstrate, using in vitro and in vivo cell proliferation, as well as colony- and tumor-forming ability and cell motility assays, that TBX2 and TBX3 have distinct roles in melanoma progression. In the tested lines, although TBX2 could promote proliferation and transformation and was required by primary melanoma cells for immortality, TBX3 was required for tumor formation and cell migration. These findings were reproducible in a human breast cancer cell line, which confirms that TBX2 and TBX3, although highly homologous, do not have redundant roles in the transformation process of cancers where they are both overexpressed. These results have important implications for the development of new cancer treatments and in particular for melanoma, which is a highly aggressive and intractable cancer. © The Author(s) 2010.
Authors & Co-Authors
Peres, Jade
South Africa, Cape Town
Faculty of Health Sciences
Davis, Emily
South Africa, Cape Town
Faculty of Health Sciences
Mowla, Shaheen B.
South Africa, Cape Town
Faculty of Health Sciences
Bennett, Dorothy C.
United Kingdom, London
St George’s, University of London
Li, Jarod
South Africa, Cape Town
Faculty of Health Sciences
Wansleben, Sabina
South Africa, Cape Town
Faculty of Health Sciences
Prince, Sharon
South Africa, Cape Town
Faculty of Health Sciences
Statistics
Citations: 83
Authors: 7
Affiliations: 2
Identifiers
Doi:
10.1177/1947601910365160
ISSN:
19476019
e-ISSN:
19476027
Research Areas
Cancer