Modulation of Androgen Receptor Signaling in Hormonal Therapy-Resistant Prostate Cancer Cell Lines
Figure 6
Proposed model for prostate cancer progression.
In normal prostate epithelial cells the AR maintains the balance between survival, differentiation and proliferation. Cooperation between TMPRSS2:ERG (or related gene fusions) and PTEN loss (of one allele in early stages), is a potential mechanism suggested to drive the transition from prostatic intraepithelial neoplasia (PIN) to prostate adenocarcinoma. These aberrations are early events in prostate cancer development and are present in a large fraction of tumors. Initiation of prostate cancer is marked by a switch from androgen-dependent survival and differentiation to androgen-responsive proliferation. As cancer progresses, the balance is tilted towards tumor growth, while genes involved in prostate differentiation and secretory function are selectively repressed and genes promoting proliferation are up-regulated. In advanced disease, this mechanism eventually culminates in poorly-differentiated fast-growing tumors. Hormonal-therapy is offered to patients with advanced invasive disease, but the tumors will eventually become resistant to androgen ablation/blockade by either adapting or bypassing the AR pathway.