Prostate cancer is a type of cancer that develops in the male reproductive system, and most prostate cancer can be slow growing. However, there are still aggressive type of prostate cancers, because the cancer cells can spread from the prostate of a patient to all other part of the body particularly the lymph nodes and bones. Initially, prostate cancer may reveal no symptom, however, in a later stage, it can cause pain, erectile dysfunction, urinating difficulty, problems in having sexual intercourse and sometimes death. Prostate cancer is common among the older men especially men reaching age of 50 and above, however, the rate of prostate cancer varies across the world. Its widespread is more frequently in Europe and the United States than in the South and East Asia. Globally, "prostate cancer is the 6th leading cause of cancer-related death in men." (Siegel, 2011, p 212). However, the prostate cancer is more common in the advanced countries than underdeveloped world. It is now the first cause of death among men in the UK and second in the United States. However, factors such as diet and genetics have been identified as the causes of prostate cancer; however, light pollution has also been identified as the cause of prostate cancer. One of the methods to establish a prostate cancer cell line is LNCaP, which is established from a human lymph node. (Schwickart Huan. Lill, et al.(2010). The study establishes research aims to enhance a greater understanding of prostate cancer.
Research Aims
1-To understand the mechanism how autophagy inhibition targets directly the ubiquitination of γH2AX.
2-Test whether shATG7 knockdown induced LNCap cells could influence γH2AX level following radio sensitivity by suppressing DNA repair.
3-To determine the interacting partner of USP14 in autophagy deficient cells.
The study reviews the related study to enhance a greater understanding of the research aims.
Review of Related Studies
"Autophagy is a self degradation process that can mediate cell death as well as survival. Autophagy induced during starvation, growth factor deprivation, hypoxia, endoplasmic reticulum (ER) stress, and microbial infection can prevent cell death" (Singh, Sharma, Mir, et al. 2014, p 13).
Kroemer, Marino, Levine, (2009) also point out that autophagy is evolved from unicellular that is capable of surviving on nutrient stress. Moreover, autophagy involves lysosomal degradation of cytosolic components. However, autophagy can be integrated in other cellular through mutual control. Autophagy can also be associated to cell death with excessive mitophagy, which lead to a loss to caspase activation as well as lysosomal membrane permeabilization.
Lock, Roy, Kenific (2010) argue that the protumorigenic functions and autophagy are attributed to the increase of cancer cell. The authors demonstrate that there is an unexpected connection between glucose and autophagy, which facilitates transformation of adhesion-independent driven by a strong oncogenic. The authors also test the effect ATG knockdown. The shATG7-2 was suspended with the absence of pepstatin A (E/P) and E64d. The results reveal the mean of ± SEM, which reveals three or more independent experiments.
Singh, (2011) point out that survival signaling and cell death are critical for the cellular response against ionizing chemotherapy and radiation in PCa (prostate cancer). Typically, Apo2L/TRAIL, and IR are widely used for the therapeutics for prostate cancer, however, resistance cellular that have been developed over time may hinder the effectiveness of therapeutics. Singh (2011) demonstrates an investigation on a response of IR (ionizing radiation) and Apo2L/TRAIL in PCa cell lines. Essentially, PC3 cells are more to cell-mediated death of Apo2L/TRAIL compared to LNCaP-derived C4-2.
However, Subramaniam et al. (2013) argue that USP14, deubiquitinating enzyme in association with the proteasome is critical to mediate ubiquitin trimming as well as ensuring ubiquitin trimming. However, ageing is associated with decline in proteasomal proteolysis, and the USP14 has a contributory role in the decline proteasomal proteolysis. The authors argue that proteasome-associated USP14 in association with the enzymatic activity is significant higher in T cell of people aged 50 and above. Thus, increase in USP14 could enhance chemically inhibiting proteasome. The authors also investigate whether the USP14 activity could regulate proteasomal proteolysis. Typically, T cells of young people shows increase degradation of I-B?, however, the T cells of elderly people are unaffected by IU1 pretreatment. The results reveal that a decrease of proteolysis of proteasomal substrates among elderly people could make elderly people to be suspectible to prostate cancer.
Essentially, the prostate cancer is common among elderly people because Proteasome associated with enzyme USP14 increase significantly with increase in age. With increase in overall cellular levels of USP14, increase in USP14 activity in the T-cells of aged people is attributed to low level of proteasomal proteolytic activity. However, Todi, & Das (2012) point out that increasingly large family of the deubiquitinases and enzymes play a critical role in health and disease, Typically, Ubiquitin is pathway to...
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