Telomerase reverse transcriptase and telomeric-repeat binding factor protein 1 as regulators of telomerase activity in pancreatic cancer cells.
Telomerase adds hexameric repeats of 5'-TTAGGG-3' termed telomeres to ends of chromosomal DNA. This enzyme has been implicated in cellular immortalization and cellular senescence. Recently, a number of relevant genes have been cloned, including these encoding three major components of human telomerase: human telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT), and telomerase-associated protein-1 (TEP1). Also important are genes encoding human telomeric-repeat binding factor protein (TRF) 1 and 2. To clarify mechanisms regulating telomerase activity, we studied telomerase activity, the telomeric restriction fragment (TRF) length and gene expression of these telomerase components and the telomeric-repeat binding factor proteins in sequential observation following X-irradiation of cultured pancreatic cancer cells. We previously reported that PANC-1 cells are better able to tolerate thermal stress, antineoplastic drugs, and exposure to tumour necrosis factor than MIAPaCa-2 cells. MIAPaCa-2 and PANC-1 cells were exposed to X-irradiation, their telomerase activity was increased at 2 days and then decreased gradually. Of the three telomerase components, only hTERT mRNA expression showed parallel changes. TRF length was stable just before and after X-irradiation. Among binding factor proteins, TRF1 mRNA showed reciprocal changes possibly directed toward maintaining a stable telomere length. In this study, our results demonstrate that not only hTERT but also TRF1 are important regulator of telomerase activity.
Yajima
T
T
Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Yagihashi
A
A
Kameshima
H
H
Kobayashi
D
D
Hirata
K
K
Watanabe
N
N
D002452:Cell Count; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*; D035321:Telomeric Repeat Binding Protein 1; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000528:radiation effects
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D035321:Telomeric Repeat Binding Protein 1; D019098:Telomerase