Human Gene Set: LINDVALL_IMMORTALIZED_BY_TERT_DN


Standard name LINDVALL_IMMORTALIZED_BY_TERT_DN
Systematic name M1561
Brief description Genes down-regulated in BJ cells (foreskin fibroblasts) immortalized by expression of TERT [GeneID=7015].
Full description or abstract Reconstitution of telomerase activity by ectopic expression of telomerase reverse transcriptase (hTERT) results in an immortal phenotype in various types of normal human cells, including fibroblasts. Despite lack of transformation characteristics, it is unclear whether hTERT-immortalized cells are physiologically and biochemically the same as their normal counterparts. Here, we compared the gene expression profiles of normal and hTERT-immortalized fibroblasts by using a cDNA microarray containing 20,736 cDNA clones and identified 172 dysregulated genes or expressed sequence tags (ESTs). One of the highly expressed genes in the hTERT-immortalized fibroblasts (hTERT-BJ cells) encodes epiregulin, a potent growth factor. Blockade of epiregulin reduced the growth of hTERT-BJ cells and colony formation of hTERT-transformed fibroblasts. Moreover, inhibition of epiregulin function in immortal hTERT-BJ cells triggered a senescence program. Our results suggest that both activation of telomerase and subsequent induction of epiregulin are required for sustained cell proliferation. Given the significant difference in gene expression profiles between normal and hTERT-immortalized fibroblasts and the close relationship between epiregulin and tumorigenesis, we conclude that hTERT-immortalized cells may not replace their normal counterparts for studies of normal cell biology and that the use of hTERT for expansion of normal human cells for therapeutic purposes must be approached with caution.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12702554   Authors: Lindvall C,Hou M,Komurasaki T,Zheng C,Henriksson M,Sedivy JM,Björkholm M,Teh BT,Nordenskjöld M,Xu D
Exact source Table 2S
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Source species Homo sapiens
Contributed by John Newman (University of Washington)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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