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Open Access Research article

The use of transformed IMR90 cell model to identify the potential extra-telomeric effects of hTERT in cell migration and DNA damage response

Xu Cao1, Chiou Mee Kong1, Kanchi Madhu Mathi1, Yoon Pin Lim1, Valere Cacheux-Rataboul2 and Xueying Wang13*

Author Affiliations

1 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Block MD4, Level 1, 5 Science Drive 2, Singapore 117545, Singapore

2 Gene Regulation Laboratory, Genome Institute of Singapore, Singapore, Singapore

3 National University Cancer Institute of Singapore (NCIS), Singapore, Singapore

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BMC Biochemistry 2014, 15:17  doi:10.1186/1471-2091-15-17

Published: 7 August 2014

Abstract

Background

Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomesase, is responsible for telomere maintenance and its reactivation is implicated in almost 90% human cancers. Recent evidences show that hTERT is essential for neoplastic transformation independent of its canonical function. However, the roles of hTERT in the process remain elusive. In the current work, we explore the extra-telomeric role of hTERT in the neoplastic transformation of fibroblast IMR90.

Results

Here we established transformed IMR90 cells by co-expression of three oncogenic factors, namely, H-Ras, SV40 Large-T antigen and hTERT (RSH). The RSH-transformed cells acquired hallmarks of cancer, such as they can grow under anchorage independent conditions; self-sufficient in growth signals; attenuated response to apoptosis; and possessed recurrent chromosomal abnormalities. Furthermore, the RSH-transformed cells showed enhanced migration capability which was also observed in IMR90 cells expressing hTERT alone, indicating that hTERT plays a role in cell migration, and thus possibly contribute to their metastatic potential during tumor transformation. This notion was further supported by our microarray analysis. In addition, we found that Ku70 were exclusively upregulated in both RSH-transformed IMR90 cells and hTERT-overexpressing IMR90 cells, suggesting the potential role of hTERT in DNA damage response (DDR).

Conclusions

Collectively, our study revealed the extra-telomeric effects of hTERT in cell migration and DDR during neoplastic transformation.

Keywords:
Extra-telomeric; hTERT; Neoplastic transformation; Cell migration; DNA damage response