The study, published in the latest issue of EMBO reports, shows that in the presence of the tumour suppressor gene, p53, dysfunctional telomeres can induce senescence whereas in the absence of p53 these abnormalities can lead to a higher incidence of cancer.

Researchers from the MD Anderson Cancer Center, studied tumour progression in p53^p/p knock-in mice that have two copies of the p53^R172P allele.

These mice were unable to induce apoptosis but could still induce cell cycle arrest and senescence pathways. The researchers showed that the activation of the p53-mediated senescence pathway was sufficient to suppress tumorigenesis.

The p53 tumour suppressor gene, also known as 'the guardian of the genome', has previously been shown to be functionally impaired in more than 60 per cent of human cancers.

The gene works by initiating cell-cycle arrest, cellular senescence or apoptosis to suppress the onset of cancer in response to genotoxic stress. However, it is unknown which function is more important for in vivo tumour suppression.

The prevalence of human cancer increases with advancing age, with most cancers occurring in older adults due to instability in the genome. This instability can be caused by a loss in the functional stability of telomeres, a repetitive TTAGGG sequence that protects the end of linear chromosomes.

Global induction of the p53 and p21 genes was observed in the mice as well as the senescence marker beta-galactosidase. The results indicate that halting cellular proliferation may act as an important tumour suppressor mechanism for many cancers.

Interestingly, the researchers found that the mechanism does not suppress carcinogen-induced skin tumorigenesis in these mice and postulate that p53-mediated apoptosis is required to suppress these malignancies.