Harmful cells’, such as cancerous cells, growth depends on evasionof apoptosis, which is considered as one of the hallmarks of cancer.Apoptosis is ultimately carried out by the sequential activation of initiatorand executioner caspases, which constitute a family of intracellularproteases involved in dismantling the cell in an ordered fashion. In cancer,therefore, one would anticipate caspases to be frequently renderedinactive, either by gene silencing or by somatic mutations. From clinicaldata, however, there is little evidence that caspase genes are impairedin cancer. Executioner caspases have only rarely been found mutatedor silenced, and also initiator caspases are only affected in particulartypes of cancer. There is experimental evidence from transgenic micethat certain initiator caspases, such as caspase-8 and -2, might act astumor suppressors. Caspase-2, the most conserved member of the caspase family, has long been recognized as an important protein inthe regulation of apoptosis. Caspase-2 is activated upon genotoxicstress in a large protein complex termed the PIDDosome (Tinel andTschopp, 2004). For this reason, we study and analyzed 2 exons of thehuman caspase-2 gene, using a strategy combining gene expressionbased RT-PCR amplification to investigate the associations betweenprostate cancer and caspase-2 gene expression in 9 individulas withprostate cancer. As a result of working, the level of variant-1 andvariant-2 of caspase-2 gene expression in prostate cancer tissues wasshown to be lower than in the control specimens and β-actin gene. Expressionlevels of β-actin were used as internal positive control. It hasbeen demonstrated that the restoration of caspase-2 deficient cancertissues augments their sensitivity to undergo apoptosis in response tochemotherapeutic agents and to other apoptotic inducers. Consistent with this, evidence is accumulating for potential roles of caspase-2 in non-apoptotic processes, including cell cycle regulation and DNA repair.In addition, a tumor-suppressor function has been suggested forcaspase-2. Here we discuss the various defects in caspases dependentcell death machinery identified in the prostate cancer specimens.
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