Fig. 1.

A schematic presentation of different pathways involved in PCa disparity.1. In the cytoplasm, testosterone is reduced to dihydrotestosterone (DHT) in the presence of 5α-reductase and binds to the androgen receptor (AR). The DHT/AR complex migrates to the nucleus and binds to androgen responsive elements (ARE) that further stimulates the activation of gene transcription. 2. After ligand interaction, receptor tyrosine kinase such as EGFR/PDGF/IGF stimulates its phosphorylation and subsequently actives PI3K and Akt pathway which further leads to the activation and migration of mTOR to the nucleus. In the nucleus, activated mTOR induces initiation of gene transcription, which results in proliferation, survival, and angiogenesis. 3. Binding of cytokines such as interleukin 6 (IL-6) to its receptor initiates several cellular events including activation of Janus kinase (JAK)/signal transducer and activating of transcription 3 (STAT3). Activated STAT3 forms homodimers that move to the nucleus and stimulates gene transcription. In brief, activation of; 1. androgen receptor, 2. receptor tyrosine kinase, and 3. Cytokine, induced downstream activation of responsive genes which are critical for PCa cells existence.