2001
DOI: 10.1073/pnas.131211098
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A low threshold level of expression of mutant-template telomerase RNA inhibits human tumor cell proliferation

Abstract: The ribonucleoprotein telomerase synthesizes telomeric DNA by copying an intrinsic RNA template. In most cancer cells, telomerase is highly activated. Here we report a telomerase-based antitumor strategy: expression of mutant-template telomerase RNAs in human cancer cells. We expressed mutant-template human telomerase RNAs in prostate (LNCaP) and breast (MCF-7) cancer cell lines. Even a low threshold level of expression of telomerase RNA gene constructs containing various mutant templates, but not the control … Show more

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Cited by 134 publications
(146 citation statements)
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“…This RNA reconstitutes a mutant holoenzyme that adds mutant repeats (T 3 G 3 ) onto the telomeres (Marusic et al, 1997;Guiducci et al, 2001;Kim et al, 2001). YCC-B1, MCF-7 and YCC-B2 cells were transfected with the vector alone or a plasmid encoding MuA-hTR and clonal populations were selected.…”
Section: Establishment Of Stable Clonal Populations Expressing a Mutamentioning
confidence: 99%
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“…This RNA reconstitutes a mutant holoenzyme that adds mutant repeats (T 3 G 3 ) onto the telomeres (Marusic et al, 1997;Guiducci et al, 2001;Kim et al, 2001). YCC-B1, MCF-7 and YCC-B2 cells were transfected with the vector alone or a plasmid encoding MuA-hTR and clonal populations were selected.…”
Section: Establishment Of Stable Clonal Populations Expressing a Mutamentioning
confidence: 99%
“…The presence of the mutant hTR was monitored by telomere repeat amplification protocol (TRAP) assays under conditions that specifically detect mutant telomerase activity (Figure 2a-c). Wild-type telomerase activity was monitored using standard TRAP conditions and was not affected by the presence of the mutant RNA (data not shown; Feng et al, 1995;Marusic et al, 1997;Kim et al, 2001). The mutant hTR was able to reconstitute an active telomerase that synthesized mutated telomeric repeats (Figure 2d and data not shown).…”
Section: Establishment Of Stable Clonal Populations Expressing a Mutamentioning
confidence: 99%
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“…[22] (unpublished data), or Trypanosoma, and could be linked to polyadenylation as seen in budding yeast [62]. Oligo dT primed RT-PCR analysis was previously used to determine the polyadenylation status of human telomerase RNA [63], and to measure the cellular concentration of yeast telomerase RNA, TLC1 [64]. Using a similar approach, we were able to identify polyadenylated TbTR transcript not only in total RNA fraction but also from immunopurified telomerase complex ( Figure 1D and Supplementary information, Figure S2B).…”
Section: Discussionmentioning
confidence: 99%
“…This approach relied on the expression of mutant telomerase RNA (TERC) molecules (Guiducci et al, 2001;Kim et al, 2001;Marusic et al, 1997). When constructs expressing TERC molecules mutated in the template region were expressed in mammalian cells, they could be complex, with endogenous hTERT and result in the incorporation of the mutant sequence into chromosomal telomeres.…”
Section: Mutant Telomerase Rnamentioning
confidence: 99%