In this study provides the relevance of cellular

In vitro cellular senescence, triggered
by activation of oncogenes has been involved in anti-tumor treatments but the
relevance of senescence against tumorigenesis is yet to be proved. Prostate
cancer involves the altercation of numerous tumor suppressor genes among which PTEN
and p53 are the most commonly mutated genes. Functionally different PTEN and
p53 are mutually dependent as PTEN provides stability to p53 and in return PTEN
gets enhancement in its transcription from p53. This study provides the
insights about the relationship between these two tumor suppressors. For this
study, mutant mice (PTEN and Trp23 deletion in prostate) were developed and
significance of cellular senescence at different conditions were studied by
employing numerous techniques such as Cre/loxP
technique for prostate-specific inactivation study, histopathological analysis
and magnetic resonance imaging(MRI) were used to study early and later effects
of inactivation of both suppressors respectively and primary mouse embryonic fibroblast
were used to investigate the basis of mutual relationship between the two
suppressors. Complete inactivation of PTEN resulted non-lethal invasive mouse prostate
cancer after 4-6 months of latency whereas Trp53 inactivation neither developed
any pathological changes in mouse prostate nor produced any tumors but it accelerated
the progression of tumor initiated by the PTEN inactivation. When PTEN and p53
both genes were inactivated, lethal invasive prostate cancer was found in mice
by the age of seven months. Furthermore, acute PTEN inactivation induced cellular
senescence through p53-mediated cellular pathway both in vivo and in vitro. Also,
cellular senescence was detected in early-stage human prostate cancer. The
findings of this study provides the relevance of cellular senescence in
restriction of tumorigenesis in
vivo.