title: Role of GLTSCR2 in the regulation of telomerase activity and chromosome stability.
abstract: Telomerase is essential for regulating telomeres, and its activation is a critical step in cellular immortalization and tumorigenesis. The transcriptional activation of human telomerase reverse transcriptase (hTERT) is critical for telomerase expression. Although several transcriptional activators have been identified, factors responsible for enhancing the hTERT promoter remain to be fully elucidated. In the present study, the role of glioma tumor-suppressor candidate region gene 2 (GLTSCR2) in telomerase regulation was analyzed. A doxycyclin-inducible green fluorescent protein (GFP)-tagged GLTSCR2-expressing adenovirus (Ad‑GLT/GFP) was used for the transduction of SK‑Hep‑1 and T98G cancer cells, and normal human umbilical vein endothelial cells. Changes in telomerase activity using telomere repeat amplification protocol assay were assessed, and the gene expression levels of hTERT were then examined. To investigate chromosome instability and senescence, Giemsa and β-galactosidase staining was performed. The results revealed that overexpression of GLTSCR2 significantly increased telomerase activity in the cancer and normal cell lines. This increase was consistent with increases in the protein and mRNA expression levels of hTERT. In luciferase assays, the hTERT promoter was activated by GLTSCR2. Knockdown of GLTSCR2 led to the downregulation of telomerase activity, abnormal nuclear morphology as a marker of chromosome instability, significant suppression of growth rate, alterations in cellular morphology and, eventually, cellular senescence. Taken together, the results of the present study suggested that GLTSCR2 is crucially involved in the positive regulation of telomerase and chromosome stability.
authors.affiliation: Department of Pathology, School of Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea.
authors.forename: Jee-Youn
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Pathology, School of Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea.
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: An
authors.affiliation: Department of Pathology, School of Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000235:genetics; D043171:Chromosomal Instability; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006801:Humans; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C500712:NOP53 protein, human; D025521:Tumor Suppressor Proteins; D019098:Telomerase