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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Ectopic Tbx2 expression results in polyploidy and cisplatin resistance
Oncogene, Volume 27, No. 7, Year 2008
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Description
T-box factors play critical roles in embryonic development and have been implicated in cell cycle regulation and cancer. For example, Tbx2 can suppress senescence through a mechanism involving the repression of the cyclin-dependent kinase inhibitors, p19ARF and p21WAF1/CIP1/SDII, and the Tbx2 gene is deregulated in melanoma, breast and pancreatic cancers. In this study, several transformed human lung fibroblast cell lines were shown to downregulate Tbx2. To further investigate the role of Tbx2 in oncogenesis we therefore stably reexpressed Tbx2 in one such cell line. Compared to their parental cells, the resulting Tbx2-expressing cells are larger, with binucleate and lobular nuclei containing double the number of chromosomes. Moreover, these cells had an increase in frequency of several features of genomic instability such as chromosome missegregation, chromosomal rearrangements and polyploidy. While grossly abnormal, these cells still divide and give rise to cells that are resistant to the chemotherapeutic drug cisplatin. Furthermore, this is shown to be neither species nor cell type dependent, as ectopically expressing Tbx2 in a murine melanoma cell line also induce mitotic defects and polyploidy. These results have important implications for our understanding of the role of Tbx2 in tumorigenesis because polyploidy frequently precedes aneuploidy, which is associated with high malignancy and poor prognosis. © 2008 Nature Publishing Group All rights reserved.
Authors & Co-Authors
Davis, Emily
South Africa, Cape Town
University of Cape Town
Teng, Huajian
South Africa, Cape Town
University of Cape Town
Bilican, B.
United Kingdom, Oxted
Marie Curie Research Institute
Parker, M. Iqbal
South Africa, Cape Town
University of Cape Town
Liu, B.
United Kingdom, Oxted
Marie Curie Research Institute
Carriera, S.
United Kingdom, Oxted
Marie Curie Research Institute
Goding, C. R.
United Kingdom, Oxted
Marie Curie Research Institute
Prince, Sharon
South Africa, Cape Town
University of Cape Town
South Africa, Cape Town
Faculty of Health Sciences
Statistics
Citations: 53
Authors: 8
Affiliations: 3
Identifiers
Doi:
10.1038/sj.onc.1210701
ISSN:
09509232
e-ISSN:
14765594
Research Areas
Cancer
Genetics And Genomics