Essential role of mouse telomerase in highly proliferative organs

@article{Lee1998EssentialRO,
  title={Essential role of mouse telomerase in highly proliferative organs},
  author={Han-Woong Lee and M. Blasco and G. Gottlieb and J. Horner and C. Greider and R. DePinho},
  journal={Nature},
  year={1998},
  volume={392},
  pages={569-574}
}
We have investigated the role of the enzyme telomerase in highly proliferative organs in successive generations of mice lacking telomerase RNA. Late-generation animals exhibited defective spermatogenesis, with increased programmed cell death (apoptosis) and decreased proliferation in the testis. The proliferative capacity of haematopoietic cells in the bone marrow and spleen was also compromised. These progressively adverse effects coincided with substantial erosion of telomeres (the termini of… Expand
Immunosenescence phenotypes in the telomerase knockout mouse
  • M. Blasco
  • Biology, Medicine
  • Springer Seminars in Immunopathology
  • 2002
TLDR
The study of the telomerase-deficient mouse model supports the notion that telomere shortening with age contributes to immunological dysfunction in the elderly. Expand
Role of telomerase in normal and cancer cells.
  • M. Meyerson
  • Biology, Medicine
  • Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2000
TLDR
The structure and function of telomeres and telomerase, the role of telomersase in cell immortalization, and the effects of telomer enzyme inactivation on normal and cancer cells are discussed and the evidence regarding whether telomerases inhibitors could be used to treat human cancers is considered. Expand
Telomere shortening and cell fates in mouse models of neoplasia.
  • S. Artandi
  • Biology, Medicine
  • Trends in molecular medicine
  • 2002
TLDR
This data indicates that telomerase-deficient mouse models of cancer have indicated that telomere shortening can exert profoundly different influences on cell fates in developing cancers, limiting tumorigenesis by enhancing cell death or facilitating carcinogenesis by compromising chromosomal stability. Expand
Telomeres, telomerase, and cancer: life on the edge of genomic stability
TLDR
The most recent biochemical and genetic evidence suggesting that telomere length maintenance by telomerase is critical to the proliferative ability of some immortalized mammalian cells in culture and in vivo is summarized. Expand
Severe growth defect in mouse cells lacking the telomerase RNA component
TLDR
Accompanying the continual telomere shortening, the growth rate of Terc-deficient ES cells was gradually reduced after more than 300 divisions, and then cell growth virtually stopped, showing that telomerase-dependent telomeres maintenance is critical for the growth of mammalian cells. Expand
Regulation of telomerase activity by apparently opposing elements
TLDR
This review summarizes the advances in understanding of the positive and negative regulation by extracellular factors of telomerase activity in cancer, stem cells and other systems in mammals. Expand
The telomerase activity of adult mouse testis resides in the spermatogonial alpha6-integrin-positive side population enriched in germinal stem cells.
TLDR
It is demonstrated here that the telomerase activity of adult mouse testis resides in the alpha6-integrin-positive Side Population containing spermatogonia and enriched in sperMatogonial stem cells. Expand
Mouse models to study the role of telomeres in cancer, aging and DNA repair.
  • M. Blasco
  • Biology, Medicine
  • European journal of cancer
  • 2002
TLDR
This review will focus on mammalian telomeres and, in particular, on the analysis of different mouse models for proteins that are important for telomere function, such as telomerase and varioustelomere-binding proteins. Expand
Complex roles for telomeres and telomerase in breast carcinogenesis
  • S. Artandi
  • Medicine, Biology
  • Breast Cancer Research
  • 2002
TLDR
In mature cancers, telomerase probably serves a crucial role in tumor progression and maintenance by stabilizing telomeres and supporting the immortal growth of breast cancer cells. Expand
Telomeres in cancer and aging: lessons from the mouse.
TLDR
These studies, which characterized mice with impaired telomere capping due to abrogation of telomeres-binding proteins, as well as their implications for putative therapies based of telomerase inhibition of telomersase re-introduction for cancer or age-related diseases, respectively are discussed. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 35 REFERENCES
Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
TLDR
Results indicate that telomerase is essential for telomere length maintenance but is not required for establishment of cell lines, oncogenic transformation, or tumor formation in mice. Expand
Extension of life-span by introduction of telomerase into normal human cells.
Normal human cells undergo a finite number of cell divisions and ultimately enter a nondividing state called replicative senescence. It has been proposed that telomere shortening is the molecularExpand
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 culturedExpand
Mechanism of telomerase induction during T cell activation.
TLDR
It is shown that the increase in telomerase activity during T cell activation was transient and did not prevent the loss of telomeres in long-term T cell cultures. Expand
hEST2, the Putative Human Telomerase Catalytic Subunit Gene, Is Up-Regulated in Tumor Cells and during Immortalization
TLDR
The cloning of a human gene, hEST2, that shares significant sequence similarity with the telomerase catalytic subunit genes of lower eukaryotes is reported, suggesting that the induction of hEST 2 mRNA expression is required for the telomersase activation that occurs during cellular immortalization and tumor progression. Expand
Developmental and tissue-specific regulation of mouse telomerase and telomere length.
  • K. Prowse, C. Greider
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1995
TLDR
It is suggested that there is tissue-specific regulation of mouse telomerase during development and aging in vivo, and most mouse tissues had active telomerases, compared to human tissues, which may reflect the ease of immortalization of primary mouse cells relative to human cells in culture. Expand
Telomeres in the mouse have large inter-chromosomal variations in the number of T2AG3 repeats.
TLDR
It is estimated that the shortest telomeres are around 10 kb in length, indicating that each mouse cell has a few telomerres with (T2AG3)n lengths within the range of human telomere lengths, which may be critical in limiting the replicative potential of murine cells. Expand
The RNA component of human telomerase
TLDR
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. Expand
Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity.
TLDR
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. Expand
Regulated expression of telomerase activity in human T lymphocyte development and activation
TLDR
The results indicate that the expression of telomerase in normal human T lymphocytes is both developmentally regulated and activation induced, and may play a permissive role in T cell development and in determining the capacity of lymphoid cells for cell division and clonal expansion. Expand
...
1
2
3
4
...