Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA

@article{Blasco1997TelomereSA,
  title={Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA},
  author={Mar{\'i}a A. Blasco and Han-Woong Lee and Manoor Prakash Hande and Enrique Samper and Peter M. Lansdorp and Ronald A. DePinho and Carol W. Greider},
  journal={Cell},
  year={1997},
  volume={91},
  pages={25-34}
}
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References

SHOWING 1-10 OF 83 REFERENCES

Telomerase activation in mouse mammary tumors: lack of detectable telomere shortening and evidence for regulation of telomerase RNA with cell proliferation

The data suggest that the mechanism of telomerase activation in mouse mammary tumors is not linked to global loss of telomere function but involves multiple regulatory events including upregulation of telomersase RNA in proliferating cells.

Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity.

The results suggest that chromosomes with short (TTAGGG)n tracts are recombinogenic, critically shortened telomeres may be incompatible with cell proliferation and stabilization of telomere length by telomerase may be required for immortalization.

Differential regulation of telomerase activity and telomerase RNA during multi-stage tumorigenesis

Results clearly demonstrate telomersase is activated in late stages of tumour progression, and show for the first time that the initial up regulation of telomerase RNA is an early event, concurrent with the hyperproliferation elicited by viral oncogenes.

Telomerase activity in normal and malignant murine tissues.

Telomerase activity during mammary tumorigenesis in transgenic mice overexpressing the neu gene was elevated in tumors versus normal tissues and was enhanced by short-term culturing of normal cells.

The RNA component of human telomerase

Human cell lines that expressed hTR mutated in the template region generated the predicted mutant telomerase activity, and cells transfected with an antisense hTR lost telomeric DNA and began to die after 23 to 26 doublings.

Telomere elongation in immortal human cells without detectable telomerase activity.

It is suggested that the presence of lengthened or stabilized telomeres is necessary for immortalization, and that this may be achieved either by the reactivation of telomerase or by a novel and as yet unidentified mechanism.

Functional characterization and developmental regulation of mouse telomerase RNA

The shorter template regions of the mouse and other rodent telomerase RNAs could account for the shorter distribution of products (processivity) generated by the mouse enzyme relative to the human telomersase.

Specific association of human telomerase activity with immortal cells and cancer.

Synthesis of DNA at chromosome ends by telomerase may be necessary for indefinite proliferation of human cells. A highly sensitive assay for measuring telomerase activity was developed. In cultured…

Increased telomerase activity in mouse skin premalignant progression.

It appears that the progressive increase in telomerase activity is associated with the increased level of genomic instability and the phenotypic progression of these premalignant tumors.

Telomeres shorten during ageing of human fibroblasts

The amount and length of telomeric DNA in human fibroblasts does in fact decrease as a function of serial passage during ageing in vitro and possibly in vivo.
...