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PAX8 Regulates Telomerase Reverse Transcriptase and Telomerase RNA Component in Glioma

¹ Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand and ² Children's Medical Research Institute, Westmead, and University of Sydney, New South Wales, Australia

Requests for reprints: Janice A. Royds, Department of Pathology, Dunedin School of Medicine, University of Otago, P.O. Box 913, Dunedin, New Zealand. Phone: 64-3479-7471; Fax: 64-3479-7136; E-mail: Janice.royds{at}stonebow.otago.ac.nz.

Key Words: PAX8 • PAX2 • Telomerase • Glioma • Transcription factor

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 (r² = 0.75, P < 0.001) and in established glioma cell lines (r² = 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. [Cancer Res 2008;68(14):5724–32]