Down-regulation of telomerase activity in malignant glioma cells by p27KIP1.
The cyclin-dependent kinase inhibitor p27KIP1 is considered not only a prognostic factor in cancer, but also a promising anti-cancer agent. However, the relationship between p27KIP1 and telomerase, that has potential as tumor-marker, remains to be elucidated. In this study, using the recombinant adenoviral vector expressing p27KIP1 (Adp27KIP1), we investigated whether p27KIP1 affects telomerase activity in malignant glioma U373-MG cells. Overexpression of p27KIP1 suppressed telomerase activity in tumor cells. The down-regulation of telomerase was due to inhibition of the human telomerase reverse transcriptase (hTERT) gene expression at the transcriptional level. This inhibitory effect was partially induced by interfering with binding sites of the hTERT core promoter for transcription factors Myc and Sp1. These findings identify a novel role for p27KIP1 in down-regulation of telomerase activity.
Kanzawa
Takao
T
Department of Neurosurgery, Mount Sinai School of Medicine, New York, NY 10029, USA.
Komata
Tadashi
T
Kyo
Satoru
S
Germano
Isabelle M
IM
Kondo
Yasuko
Y
Kondo
Seiji
S
D001665:Binding Sites; D001932:Brain Neoplasms / Q000201:enzymology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005910:Glioma / Q000201:enzymology*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016329:Sp1 Transcription Factor; D019098:Telomerase / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; D016329:Sp1 Transcription Factor; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008156:Luciferases; D019098:Telomerase