There steroid hormone receptor and composed of four

There are various kind of molecular pathways are
playing critical role to induce the development of cancer such as AR mediated
signalling, PI3K/AKT pathway, NF-kB signalling, and etc. First of all, AR
(androgen receptor) mediated signalling pathway is crucial to maintain the
normal function of prostate, helps to initiate and maintain spermatogenesis. AR
is a member of steroid hormone receptor and composed of four functional
domains, which are N-terminal domain (NTD), deoxyribonucleic acid-binding
domain (DBD), ligand-binding domain (LBD) and short amino acid sequence. The
role of NTD is acts as transcription activator while DBD is to maintain
integrity of the dimerization and to stabilize AR-DNA complex. LBD is the site
which allows the steroid hormone to act on and short amino acid consists of
hinge region which segregate the LBD from DBD, including the function of
ligand-dependent nuclear localization signal for AR nuclear transport. When
there is no ligand, AR remains in the cytoplasm and associated with heat shock
proteins and other chaperones. Vice versa, when ligand binds to AR, this
complex will trigger alteration in conformation of LBD, and this fosters the
intramolecular and intermolecular interaction between N-terminal and C-terminal
domains. As a result, dimerization, phosphorylation and nuclear translocation
can occur. The complex within ligand and AR will recognize and bind to androgen
response elements in promoter and enhancer regions of target genes which then
modulate gene expression. The occurrence of prostate cancer is contributed by
deregulation of AR signalling. Castration-resistant prostate cancer (CRPC)
progression is due to overexpression of AR triggered by aberrant
post-translational modification, generation of AR splice variants and so on.
Additionally, point mutation in AR increased AR activity drastically in
prostate environment has made the ligand pool to be broader whereby AR can
respond to. Moreover, growth factors like insulin-like growth factor-1 (IGF-1),
VEGF and other cytokines advocates synergistic activities of AR and this
phenomenon can cause prostate cancer. At last, mutated co-repressors and
co-activators molecules will galvanize AR activation and then develop into
prostate cancer. 

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