April 2, 2007
Research Shows Mechanism For Arresting Tumor GrowthTopics: Medical Science News
New research by scientists from the MD Anderson Cancer Center has shown that inducing senescence, a state of permanent cell-cycle arrest, may be sufficient to guard against cancer development in aged cells. The study shows that in the presence of the tumor suppressor gene, p53(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), dysfunctional telomeres can induce senescence whereas in the absence of p53 these abnormalities can lead to a higher incidence of cancer. In other words, activation of the p53-mediated senescence pathway was sufficient to suppress tumorigenesis:
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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, there is a relationship between p53, telomeres, telomerase, and cancer. The clinical relevance of telomeres is that a cancer cell, unlike a normal cell, can repair eroded telomeres. The existence of this repair mechanism suggests a novel target for cancer.
... in vitro interactions between telomerase and p53 suggest that the activity of telomerase may be regulated by p53, down-regulation of which in turn would favor up-regulation of telomerase activity in cancer cell development.
Since telomerase is not associated with benign tumors (making it a marker for malignant tumors), and since results from the M.D. Anderson research - and that of others(... in the absence of p53, chromosomal aberrations resulting from telomerase deficiency and telomere shortening accelerate development of tumors that otherwise would have been prevented by p53-dependent cell cycle arrest or apoptosis triggered by these chromosomal changes), further demonstrates the importance of the p53 pathway in tumor suppression, we can count ourselves yet another step closer toward the development of new drugs for treating cancer.
Molecular interactions between telomerase and the tumor suppressor protein p53 in vitro
Scientists isolate telomerase as cancer drug target
Increased p53 activity does not accelerate telomere-driven ageing
Related info: Telomerase is a specialized RNA-directed DNA polymerase that extends telomeres of eukaryotic chromosomes, has been implicated as playing an important role in cell survival. The activity of telomerase is repressed in many human somatic tissues, whereas the enzyme is activated during tumor progression in most human cancers
Posted by Richard at April 2, 2007 1:43 PM
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