Telomerase: anti-cancer target or just a fascinating enzyme?
Chemistry & BiologyPublished 1 January 1996Open access
Susan E. Hamilton, David R. Corey
Citations22
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TL;DR
Telomerase activity is upregulated in most types of malignant tumor and highly selective small molecule inhibitors will be needed to understand the biological basis for this observation and to determine if telomerase is a viable target for chemotherapy.
Abstract
Telomerase activity is upregulated in most types of malignant tumor. Highly selective small molecule inhibitors will be needed to understand the biological basis for this observation and to determine if telomerase is a viable target for chemotherapy.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
ScienceSpecific Association of Human Telomerase Activity with Immortal Cells and Cancer
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Molecular and Cellular BiologyStructure and variability of human chromosome ends.
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Data indicate that human telomerase is not restricted to immortal cells and suggest that the somatic expression of this enzyme may be more widespread than was previously inferred from the decline of human telomeres.
Proceedings of the National Academy of SciencesTelomerase activity in human ovarian carcinoma.
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It is reported that extremely short telomeres are maintained in metastatic cells of epithelial ovarian carcinoma and that tumor cells, but not isogenic nonmalignant cells, express telomerase, suggesting that progression of malignancy is ultimately dependent upon activation of telomersase and that telomerases inhibitors may be effective antitumor drugs.
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620 Citations1995Eiso Hiyama, Keiko Hiyama +4 more
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It is reported that telomerase activity is associated with prostate cancer but absent in the benign disease and normal gland, and Telomerase is, therefore, a potential diagnostic marker for prostate cancer.
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Functional analysis showed that the sequence 5' CAAAACCCCAAA 3' in this RNA is the template for synthesis of telomeric TTTTGGGG repeats by the Euplotes telomerase, and Telomerase can now be defined as a specialized reverse transcriptase.
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It is proposed that telomere lengths in these T- and B-cell lines are determined by both telomersase and telomerase-independent mechanisms.
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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.
Proceedings of the National Academy of SciencesActivation of telomerase in a human tumor.
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CellPurification of tetrahymena telomerase and cloning of genes encoding the two protein components of the enzyme
250 Citations1995Kathleen Collins, Ryûji Kobayashi +1 more
The purification of telomerase and the cloning of cDNAs encoding two protein subunits from the ciliate Tetrahymena are described and two proteins of 80 and 95 kDa copurified and coimmunoprecipitated with telomersase activity and the previously identified TetrahYmena telomerases RNA are identified.
CellA conserved secondary structure for telomerase RNA
239 Citations1991Daniel P. Romero, Elizabeth H. Blackburn
A phylogenetic comparative analysis of telomerase RNAs from seven tetrahymenine ciliates revealed a strikingly conserved secondary structure that contains the telomeric templating region.
The LancetTelomerase activity in human brain tumours
220 Citations1995Lauren A. Langford, Mieczyslaw A. Piatyszek +2 more
A distinct subgroup of brain tumour consists of transformed yet pre-immortal cells that follow different pathways of neoplastic progression, according to analysis of telomerase activity in 90 human gliomas.
NatureRecognition of a chromosome truncation site associated with α-thalassaemia by human telomerase
204 Citations1991Gregg B. Morin
Using an in vitro assay, it is shown that human telomerase correctly recognizes the chromosome 16 breakpoint sequence and adds (TTAGGG)n repeats, which seem to define two modes of DNA recognition by telomersase.
Nature BiotechnologyRefining the telomere-telomerase hypothesis of aging and cancer
168 Citations1996Shawn E. Holt, Jerry W. Shay +1 more
An overview of some of the areas that have not been well explained of the telomere-telomerase hypothesis of aging and cancer is presented to indicate where multiple interpretations of the data are possible.
Molecular and Cellular BiologyTelomerase Activation in Mouse Mammary Tumors: Lack of Detectable Telomere Shortening and Evidence for Regulation of Telomerase RNA with Cell Proliferation
157 Citations1996Dominique Broccoli, Lucy A. Godley +3 more
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.
Nucleic Acids ResearchThe effects of nucleoside analogs on telomerase and telomeres in<i>Tetrahymena</i>
121 Citations1994Catherine Strahl, Elizabeth H. Blackburn
The effects of various nucleoside analogs, known to be chain-terminating inhibitors of retroviral reverse transcriptases, on Tetrahymena thermophila telomerase activity in vitro, are analyzed and AZT decreased the efficiency of programmed de novo telomere addition during macronuclear development in mating cells.
PubMedIncreased telomerase activity in mouse skin premalignant progression.
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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.
CancerGerontology as oncology. Research on aging as the key to the understanding of cancer
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This review considers two possible explanations for the exponential increase in most neoplasms in the elderly, arguing in favor of the idea that tumor progression proceeds at faster rates in older mice and older persons than in younger mice and younger persons.
Current Opinion in Cell BiologyStructure and function of telomerase
77 Citations1996Kathleen Collins
The study of eukaryotic telomeres at the molecular level began with the discovery of short, tandem repeats at Tetrahymena chromosome ends with major insights about telomere structure and function coming from investigations of telomerase, the DNA polymerase that synthesizes these repeats.
The EMBO JournalArchitecture of telomerase RNA.
73 Citations1994Arinjita Bhattacharyya, Elizabeth H. Blackburn
A ‘two‐domain’ structure is proposed for the telomerase RNA based on function: one conformationally flexible domain, which includes the template and the region around helix III, involved with enzymatic function, and a second largely helical domain, including helices I and IV and the proposed kink, which may serve as a scaffold for protein binding.
Clinical Neurology and NeurosurgeryTelomerase activity in human brain tumors
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