PAX8 regulates telomerase reverse transcriptase and telomerase RNA component in glioma.
Paired box (PAX) developmental genes are frequently expressed in cancers and confer survival advantages on cancer cells. We have previously found that PAX genes are deregulated in glioma. We have now investigated the expression of PAX genes in glioma and their role in telomere maintenance. The mRNA level of PAX8 showed a positive correlation with telomerase activity in glioma biopsies (r(2) = 0.75, P < 0.001) and in established glioma cell lines (r(2) = 0.97, P = 0.0025). We found that PAX8 is able to coordinately transactivate the promoter for both the telomerase catalytic subunit (hTERT) and the telomerase RNA component (hTR) genes. By electrophoretic mobility shift assay, quantitative PCR, and a telomerase activity assay, we show that PAX8 binds directly to the hTERT and hTR promoters, up-regulating hTERT and hTR mRNA, as well as telomerase activity. Additionally, PAX8 small interfering RNA down-regulated hTERT and hTR. Collectively, these results show that PAX8 may have a role in telomerase regulation.
Chen
Yu-Jen
YJ
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Campbell
Hamish G
HG
Wiles
Anna K
AK
Eccles
Michael R
MR
Reddel
Roger R
RR
Braithwaite
Antony W
AW
Royds
Janice A
JA
D001483:Base Sequence; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D019098:Telomerase / Q000378:metabolism*; D015533:Transcriptional Activation
D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase