Document Detail


Alternative lengthening of telomeres in the human adrenocortical carcinoma cell line H295R.
MedLine Citation:
PMID:  16820888     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Telomere maintenance can occur in the absence of telomerase by a mechanism referred to as alternative lengthening of telomeres (ALT). ALT is considered to be rare in tumors of epithelial origin. The biological significance and molecular mechanism of ALT have not been well studied in human cancers. It has been reported that clinical samples of adrenocortical carcinoma show a low incidence of telomerase positivity. We characterized an adrenocortical carcinoma cell line, H295R, focusing on the telomere maintenance mechanism, and compared it with telomerase-positive 293 cells and HeLa cells. Telomerase activity could not be detected in H295R cells by the TRAP assay. Among the essential components of the telomerase holoenzyme, only hTERT expression was undetectable by RT-PCR, indicating that the lack of telomerase activity is due to suppression of hTERT. H295R cells had long and heterogeneous telomere DNA, and FISH revealed large nuclear bodies in a few interphase nuclei, which presumably represented ALT-associated PML bodies. These results suggest that H295R cells have the ALT phenotype. Several proteins that are possibly associated with the telomere maintenance mechanism were examined. TRF1 and TRF2 were expressed in H295R cells as well as in 293 cells and HeLa cells. The ratio of hnRNP B1 to A2 was higher in H295R cells than in 293 cells and HeLa cells. In conclusion, the H295R adrenocortical carcinoma cell line is negative for telomerase and maintains its telomeres by the ALT mechanism. We anticipate that H295R cells will be a good model for understanding the significance and mechanism of ALT in human cancers.
Authors:
Masachika Fujiwara; Hiroshi Kamma; Wenwen Wu; Yukiko Yano; Shinsuke Homma; Hiroaki Satoh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  29     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-05     Completed Date:  2006-12-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  445-51     Citation Subset:  IM    
Affiliation:
Department of Pathology, Kensei General Hospital, Iwase, Nishi-Ibaraki, Ibaraki 309-1295, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adrenal Cortex Neoplasms / pathology,  ultrastructure*
Carcinoma / pathology,  ultrastructure*
Cell Line, Tumor
Cell Nucleus / metabolism
Hela Cells
Humans
In Situ Hybridization, Fluorescence
Neoplasms / metabolism
Oligonucleotides / chemistry
Phenotype
Reverse Transcriptase Polymerase Chain Reaction
Telomerase / metabolism
Telomere / pathology,  ultrastructure*
Chemical
Reg. No./Substance:
0/Oligonucleotides; EC 2.7.7.49/Telomerase

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