| Popis: |
Primary mammalian cells reach replicative exhaustion after several passages in vitro, a process called replica- tive senescence. During such a state of permanent growth arrest, senescent cells are refractory to physiological prolifera- tion stimuli with altered cell morphology and gene expression patterns, although they remain viable with preserved meta- bolic activity. Interestingly, senescent cells have also been detected in vivo in human tumors, particularly in benign le- sions. Tumor suppressor genes are closely involved in senescence, as their knockdown and ectopic expression confer im- mortality and senescence induction, respectively. By using high throughput genetic screenings to search for genes in- volved in senescence, several candidate oncogenes and putative tumour suppressor genes have been isolated recently, in- cluding subtypes of miRNAs. Senescence is thus an anti-tumorigenic mechanism for avoidance of indefinite cell prolif- eration when an oncogenic alteration has occurred. In this review, we remark how these findings offer new perspectives in the modulation of senescence and open new approaches for cancer therapy. |
