title: The use of transformed IMR90 cell model to identify the potential extra-telomeric effects of hTERT in cell migration and DNA damage response.
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.
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
authors.forename: Chiou Mee
authors.initials: CM
authors.lastname: Kong
authors.forename: Kanchi Madhu
authors.initials: KM
authors.lastname: Mathi
authors.forename: Yoon Pin
authors.initials: YP
authors.lastname: Lim
authors.forename: Valere
authors.initials: V
authors.lastname: Cacheux-Rataboul
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Block MD4, Level 1, 5 Science Drive 2, Singapore 117545, Singapore. bchwxy@nus.edu.sg.
authors.forename: Xueying
authors.initials: X
authors.lastname: Wang
mesh_terms: D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D048708:Cell Growth Processes / Q000235:genetics; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D000072200:Ku Autoantigen; D046228:Microarray Analysis; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D000952:Antigens, Polyomavirus Transforming; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C509186:TERT protein, human; D019098:Telomerase; C000606509:Xrcc6 protein, human; D018631:ras Proteins; D000072200:Ku Autoantigen
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