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Ectopic Tbx2 expression results in polyploidy and cisplatin resistance
1Division of Cell Biology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, Western Province, South Africa.
Oncogene
|August 19, 2007
Summary
Reintroducing T-box 2 (Tbx2) into lung cancer cells caused genomic instability, including polyploidy and resistance to chemotherapy. These findings highlight Tbx2's role in oncogenesis and poor patient prognosis.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- T-box factors, including Tbx2, are crucial in development and implicated in cancer.
- Tbx2 represses cell cycle inhibitors and is deregulated in various cancers, such as melanoma and breast cancer.
- Transformed human lung fibroblast cell lines were observed to downregulate Tbx2.
Purpose of the Study:
- To investigate the role of Tbx2 in oncogenesis by reexpressing it in a Tbx2-downregulated cell line.
- To determine the effects of Tbx2 reexpression on cellular morphology, genomic stability, and drug resistance.
Main Methods:
- Stable reexpression of Tbx2 in transformed human lung fibroblasts.
- Analysis of cell size, nuclear morphology, chromosome number, and genomic instability markers.
- Assessment of resistance to cisplatin chemotherapy.
- Ectopic Tbx2 expression in a murine melanoma cell line to confirm species and cell type independence.
Main Results:
- Tbx2-expressing cells exhibited larger size, binucleate and lobular nuclei, and doubled chromosome numbers compared to parental cells.
- Increased frequencies of chromosome missegregation, rearrangements, and polyploidy were observed in Tbx2-expressing cells.
- These abnormal cells divided and developed resistance to cisplatin.
- Similar mitotic defects and polyploidy were induced by Tbx2 in a murine melanoma cell line.
Conclusions:
- Tbx2 reexpression induces significant genomic instability, including polyploidy, in cancer cell lines.
- Polyploidy induced by Tbx2 is linked to chemoresistance and may precede aneuploidy, a marker of malignancy.
- These findings underscore Tbx2's role in tumorigenesis and its association with poor prognosis.
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