Telomere maintenance in telomerase-positive human ovarian SKOV-3 cells cannot be retarded by complete inhibition of telomerase
作者:, Jessie L. -S Au
摘要:Abstract The two known mechanisms for telomere maintenance in eukaryocytes are telomerase in telomerase-positive cells and alternative lengthening of telomeres (ALT) in telomerase-negative cells. We report here that telomere maintenance in the telomerase-positive human ovarian SKOV-3 cells was not affected by inhibition of telomerase. For comparison, the effect of telomerase inhibitors on telomere maintenance in another telomerase-positive cell line (i.e. human pharynx FaDu cells) and the telomerase-negative human osteosarcoma Saos-2 cells was examined. Telomerase activity was measured using a modified telomeric repeat amplification protocol and telomere length was measured using a solution hybridization-based method and fluorescence in situ hybridization. A reverse transcriptase inhibitor (3′-azido-deoxythymidine or AZT) and an antisense against a component of human telomerase RNA (antisense hTR) were used to inhibit telomerase. FaDu and SKOV-3 cells showed comparable baseline telomerase activity. Telomerase activity in both cells was inhibited about equally by AZT (maximal inhibition of ∼80%) and by expression of antisense hTR (complete inhibition in SKOV-3 cells and maximal inhibition of ∼80% in FaDu cells). However, treatment with telomerase inhibitors resulted in ∼50% telomere shortening in FaDu cells but had no effect on SKOV-3 nor Saos-2 cells. SKOV-3 cells did not show the characteristic features of ALT (i.e. heterogeneous telomere length and promyelocytic leukemia bodies), whereas these ALT features were observed in Saos-2 cells. Collectively, these results suggest the existence of a telomerase-independent mechanism of telomere maintenance in the telomerase-positive SKOV-3 cells.
关键词:Telomerase; Telomere; Ovarian cancer; Alternative lengthening of telomeres; ALT alternative lengthening of telomeres; alternative lengthening of telomeres; AZT 3′-azido-deoxythymidine; 3′-azido-deoxythymidine; FISH fluorescence in situ hybridization; fluorescence in situ hybridization; hTR human telomerase RNA component; human telomerase RNA component; IPTG isopropyl-β-D-thiogalactopyranoside; isopropyl-β-D-thiogalactopyranoside; NHEJ non-homologous end joining; non-homologous end joining; PML promyelocytic leukemia; promyelocytic leukemia; TERT telomerase reverse transcriptase; telomerase reverse transcriptase; TRAP telomeric repeat amplification protocol; telomeric repeat amplification protocol
论文方向:[{"id":13,"name":"细胞生物学"},{"id":879,"name":"生物化学"}]
发表期刊:FEBS Letters Volume 527, Issues 1–3
发表时间:Wed Sep 11 00:00:00 CST 2002
数字识别码:10.1016/S0014-5793(02)03141-1
是否作者本人: 否
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