Abstract
Despite extensive attempts to reveal downstream genes of androgen recepter (AR) signaling in each stage of prostate cancer (PCa), the critical switches that trigger PCa leading to castration resistant PCa (CRPC) and metastasis still remain unclear. Compared to the normal prostate, proliferation/cell cycle/apoptosis related genes are upregulated, but genes related to differentiation and secretory functions are downregulated by androgen/AR in PCa. After the androgen deprivation therapy (ADT), AR becomes less sensitive to androgens, but may be able to be activated via multiple ways, such as androgen-independent AR activation, non-genotropic activation of AR, chromosome rearrangement, and cofactor activation, all of these cross-talks may contribute to the progression at the castration resistant stage with metastasis.
Distinct sets of genes up- and downregulated by AR were demonstrated in the metastatic stage. More adhesion related molecules are upregulated in metastasis. Considering different functions of AR in PCa growth (promoter) versus metastasis (suppressor), understanding the exact downstream gene profiles of AR signaling in each stage of PCa is essential so that we can develop successful future therapies with better efficacy in each stage.
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Lee, S.O., Huang, CK., Jie, L., Chang, C. (2013). Androgen Receptor-Regulated Genes in Prostate Cancer Initiation Versus Metastasis. In: Wang, Z. (eds) Androgen-Responsive Genes in Prostate Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6182-1_10
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