Dual roles of telomere dysfunction in initiation and suppression of tumorigenesis

Journal Article · Tue Jun 10 04:00:00 EDT 2008 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2008.03.011· OSTI ID:21128188

Cosme-Blanco, Wilfredo ^[1]; Chang, Sandy ^[1]

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1. Department of Cancer Genetics, Box 1006, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030 (United States)

Human carcinomas arise through the acquisition of genetic changes that endow precursor cancer cells with a critical threshold of cancer-relevant genetic lesions. This complex genomic alterations confer upon precursor cancer cells the ability to grow indefinitely and to metastasize to distant sites. One important mechanism underlying a cell's tumorigenic potential is the status of its telomere. Telomeres are G-rich simple repeat sequences that serve to prevent chromosomal ends from being recognized as DNA double-strand breaks (DSBs). Dysfunctional telomeres resemble DSBs, leading to the formation of dicentric chromosomes that fuel high degrees of genomic instability. In the setting of an intact p53 pathway, this instability promotes cellular senescence, a potent tumor suppressor mechanism. However, rare cells that stochastically lose p53 function emerge from this sea of genomic instability and progress towards cancer. In this review, we describe the use of mouse models to probe the impact of dysfunctional telomeres on tumor initiation and suppression.

• OSTI ID: 21128188
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 9 Vol. 314; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOMAS
DICENTRIC CHROMOSOMES
DNA
INHIBITION
MICE
STRAND BREAKS
TELOMERES