Category — cancer

Judith Campis and Fabrizio d’Adda di Fagagna; Nature Reviews | Molecular Cell Biology Volume 8 | 729

Cells continually experience stress and damage from exogenous and endogenous sources, and their responses range from complete recovery to cell death. Proliferating cells can initiate an additional response by adopting a state of permanent cell-cycle arrest that is termed cellular senescence. Understanding the causes and consequences of cellular senescence has provided novel insights into how cells react to stress, especially genotoxic stress, and how this cellular response can affect complex organismal processes such as the development of cancer and ageing.

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Baerlocher GM, Vulto I, de Jong G, Lansdorp PM Terry Fox Laboratory, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, V5Z 1L3, Canada. . Nat Protoc. 2006;1(5):2365-76.

Telomeres have emerged as crucial cellular elements in aging and various diseases including cancer. To measure the average length of telomere repeats in cells, we describe our protocols that use fluorescent in situ hybridization (FISH) with labeled peptide nucleic acid (PNA) probes specific for telomere repeats in combination with fluorescence measurements by flow cytometry (flow FISH). Flow FISH analysis can be performed using commercially available flow cytometers, and has the unique advantage over other methods for measuring telomere length of providing multi-parameter information on the length of telomere repeats in thousands of individual cells. The accuracy and reproducibility of the measurements is augmented by the automation of most pipetting (aspiration and dispensing) steps, and by including an internal standard (control cells) with a known telomere length in every tube. The basic protocol for the analysis of nucleated blood cells from 22 different individuals takes about 12 h spread over 2-3 days.

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Sheila A. Stewart – Departments of Cell Biology and Physiology and of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, and Robert A. Weinberg – Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142. Annu Rev Cell Dev Biol. 2006;22:531-57

The cell phenotypes of senescence and crisis operate to circumscribe the proliferative potential of mammalian cells, suggesting that both are capable of operating in vivo to suppress the formation of tumors. The key regulators of these phenotypes are the telomeres, which are located at the ends of chromosomes and operate to protect the chromosomes from end-to-end fusions. Telomere erosion below a certain length can trigger crisis. The relationship between senescence and telomere function is more complex, however: Cell-physiological stresses as well as dysfunction of the complex molecular structures at the ends of telomeric DNA can trigger senescence. Cells can escape senescence by inactivating the Rb and p53 tumor suppressor proteins and can surmount crisis by activating a telomere maintenance mechanism. The resulting cell immortalization is an essential component of the tumorigenic phenotype of human cancer cells. Here we discuss how telomeres are monitored and maintained and how loss of a functional telomere influences biological functions as diverse as aging and carcinogenesis.

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J National Cancer Inst. ;95(16)1211-18. Wu X, Amos CI, et. al.

Conclusion: “Short telomeres appear to be associated with increased risks for human bladder, head and neck, lung, and renal cell cancers.”

J National Cancer Inst. ;95(16)1211-18. Wu X, Amos CI, et. al.

Conclusion: “Short telomeres appear to be associated with increased risks for human bladder, head and neck, lung, and renal cell cancers.”

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Calvin B. Harley, Geron Corporation, Menlo Park, CA 94025, USA. Oncogene, 2002.

In the decade since the telomere hypothesis of cellular aging was proposed, the two essential genes for human telomerase were cloned and characterized, allowing experimental proof of the causal relationships between telomere loss and replicative senescence, and telomerase activation and immortalization. These relationships were established using a variety of cultured human cell types from both normal and tumor tissues, and were largely confirmed in the telomerase knockout mouse. Taken together, the data provide strong support for the potential utility of telomerase detection and inhibition for cancer, and telomerase activation for degenerative diseases.

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