Functional analyses revealed their contribution to prostate carcinogenesis by targeting relevant pathways and gene regulation mechanisms including PTEN/AKT and androgen receptor signaling as well as chromatin remodeling complexes.
Therefore, the regulation of AR protein stability and its degradation is another interesting path that could enhance our knowledge of carcinogenesis and tumor evolution possibly leading to novel therapeutic targets.
The androgen receptor (AR) is expressed in many cell types and the androgen/AR signaling has been found to have important roles in modulating tumorigenesis and metastasis in several cancers including prostate, bladder, kidney, lung, breast and liver.
Somatic reductions of the androgen receptor CAG repeat thus occur frequently, through a pathway distinct from microsatellite instability and early during colon carcinogenesis.
Although somatic alterations in CAG repeats in the androgen receptor (AR) gene have been suggested to predispose to colorectal cancer, less is known about AR in colorectal cancer carcinogenesis.
These findings suggest that expansions of the CAG repeat in the androgen receptor gene may play an important role in the carcinogenesis of uterine endometrial cells.
Androgen receptor (AR) stimulators, such as androgen and Tip60, play a pivotal role in prostatic carcinogenesis as androgen receptor signaling is critical for the growth and transformation of the prostate gland.
ETS status influences the transcriptional repertoire of the AR, and ETS- PCa tumors appear to rely on distinctly different AR-dependent transcriptional programs to drive and sustain tumorigenesis.
Expert opinion: AR activation is likely to correlate with the promotion of urothelial carcinogenesis and cancer outgrowth as well as resistance to conventional therapies.
Since androgen receptor (AR) plays a central role in PCa carcinogenesis and progression, it is imperative to systematically elucidate the causal association between AR and miRNAs, focusing on the molecular mechanisms by which miRNAs mediate AR signalling.
Interestingly, the androgen receptor (AR), already known to play a significant role in prostate cancer tumorigenesis, has recently been implicated in the processes resulting in gene fusions by inducing the spatial proximity of genes involved in rearrangements, promoting the formation of double-strand DNA breaks (DSB), and facilitating the recruitment of proteins for non-homologous end-joining (NHEJ).
The androgen receptor (AR) pathway is critical for prostate cancer carcinogenesis and development, however, after 18-24 months of AR blocking therapy, patients invariably progress to castration-resistant prostate cancer (CRPC), which remains an urgent problem to be solved.
Interestingly, three major subgroups of genomic subcomplexes were identified, where selective gain of function for AR genomic action in tumorigenesis was found, dictated by FOXA1 and HOXB13.
The present study describes a physiologically relevant in vitro model for studying the molecular mechanisms by which stroma-derived HGF and hyaluronan influence androgen receptor and CD44 functions in the secretory epithelia during prostate carcinogenesis.