Firstly, proliferation is boosted. According to Figure 4,

            Firstly,AR (androgen receptor) mediated signalling pathway is vital for keeping thehealthy state of prostate, which serve as the organ for spermatogenesis. Testessynthesized testosterone, a male steroid hormone and diffuse to the cytoplasm.After arrival to cytosol, the conversion into dihydrotestosterone (DHT) ispromoted by 5?-reductase, cytochrome P450 enzyme (da Silva et al.

, 2013). DHThas high affinity of binding to AR which then activates the entire signalling pathwayafter migration into nucleus. AR is a steroid hormone receptors, which ismake up by 4 functional domains. They are N-terminal domain (NTD),deoxyribonucleic acid-binding domain (DBD), ligand-binding domain (LBD) andshort amino acid sequence. NTD is a transcription activator while DBD is usedto maintain integrity of the dimerization and to stabilize AR-DNA complex (Ramalingam,Ramamurthy and Njar, 2017). Steroid hormone can act on the site which known asLBD. Short sequence of amino acid functions as divider to segregate LBD fromDBD. Other than that, the amino acid also aids in enhancing the nuclearlocalization signal (NLS) for AR nuclear transport (Ramalingam, Ramamurthy andNjar, 2017).

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Basically, when there is absence of ligand, AR stayed inside thecytoplasm and connected with heat shock proteins (HSP) and other chaperones.Vice versa, once the ligands bind to AR, it will change the conformation of LBDand this alteration fosters the intramolecular and intermolecular forcesbetween N-terminal and C-terminals domains (Ramalingam, Ramamurthy and Njar,2017). As a result, dimerization and phosphorylation are occurred instantly andfollowed by nuclear transport of AR. The complex within ligand and AR recognizeand bind to androgen response elements (ARE) in promoter and enhancer regionsof target genes. As a consequence, gene expression involved in cellproliferation is boosted. According to Figure 4, the occurrence of prostatecancer is contributed by the deregulation of AR signalling. Most of the time,prostate cancer progression is due to the overexpression of AR and thisabnormal condition will trigger the post-translational modifications,generation of AR splice variants and etc (Ramalingam, Ramamurthy and Njar,2017). When there are crowds of DHT-AR complex formed in the cytoplasm, thisdirectly amplified the AR expression when they succeed to migrate into nucleus.

This fastens the cell proliferation by the higher rate of transcriptionactivation. Furthermore, formation of ligand-independent AR will bring theeffect of higher rate of survival cell production. The activated AKT initiatedthe AR formation and activated them due to the cross-talk mechanism. Theactivated AR will move into nucleus which then bind on ARE and the genetranscription can begin and make the cancerous cells to divide continuously anduncontrollably. At last, AR molecules in the cytosol sometimes are susceptibleto mutation and cause other ligand can be bind with. This aberrant conditioncan raise AR activity drastically in prostate environment and encourage theformation of mutated but activated complex has high ability to transport itselfinto nucleus.

All these factors lead to proliferation and increased the growthrate which then galvanize AR activation and then develop into prostate cancer.