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Mouse Model: Telomeres and Telomerase in Stem Cell and Cancer

  • Chapter
Telomeres and Telomerase in Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Ageing is characterized by declines of adult stem cell function and regenerative reserves. The telomere has been regarded as a mitotic clock that controls cellular ageing. Telomeres are nucleoprotein complexes that consist of simple DNA repeats and associated binding proteins. In the absence of telomerase activity, telomere shortening occurs with each round of cell division. Critically short telomeres (dysfunctional telomeres) can be detected as DNA double strand breaks, thus activating DNA damage pathway and lead to cell cycle arrest, or, in some cases, apoptosis. Independent lines of evidence indicate that telomere dysfunction induces both cell intrinsic checkpoint and cell extrinsic checkpoint leading to an age-associated stem cell dysfunction. Genetically modified mice lacking telomerase activity proved an invaluable model for probing the in vivo consequences of replicative senescence and telomere-based stem cell ageing. Disturbing genes that regulate DNA damage checkpoints in response to telomere dysfunction partially rescued the degenerative phenotypes and ageing of adult stem cells, but in some cases increased tumorigenesis. Emerging evidence indicates that fine-tuning DNA damage checkpoints in response to telomere dysfunction could improve adult stem cell function, and meanwhile keep the tumor suppression mechanisms intact. Therefore, understanding the in vivo function of genes regulating telomere dysfunction during ageing could have important implication for regenerative medicine and cancer therapies.

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  1. Institute of Laboratory Animal Sciences, Max Planck Partner Group Program on Stem Cell and Aging, Chinese Academy of Medical Sciences, Beijing, China

    Xin Huang & Zhenyu Ju

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  1. Xin Huang
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  1. Dept. Translational Cancer Research, Hiroshima University, 1-2-3 Kasumi, Hiroshima, Minami-Ku, 734-8551, Japan

    Keiko Hiyama

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Huang, X., Ju, Z. (2009). Mouse Model: Telomeres and Telomerase in Stem Cell and Cancer. In: Hiyama, K. (eds) Telomeres and Telomerase in Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60327-879-9_6

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