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. 2008 Winter;8(4):213-8.

Pathogenesis of prostate cancer: lessons from basic research

Vamsidhar Velcheti, Satish Karnik, Stephen F Bardot, Om Prakash

Pathogenesis of prostate cancer: lessons from basic research

Vamsidhar Velcheti et al. Ochsner J. 2008 Winter.

Abstract

In the United States, prostate cancer is the second most common cause of cancer-related deaths in men. While the importance of androgens and androgen receptors (ARs) in primary prostate cancer is well established, the role of ARs in prostate cancers that emerge despite androgen ablation therapies remains poorly understood. The aim of this article is to illustrate the fundamental biology of prostate cancer. We focus mainly on the AR because of its critical role in the progression and metastatic spread of prostate cancer. We also summarize the alternate pathways that may potentially contribute to the progression of prostate cancer. Identifying the underlying mechanisms of androgen independence is crucial in the design of appropriate therapies for hormone-refractory neoplasms.

Keywords: adenocarcinoma; androgen receptor; hormone resistance; prostate; signaling pathways; testosterone.

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Figures

Figure 1
Figure 1. Schematic representation of the human androgen receptor. The relative locations of the amino-terminal domain (NTD), the DNA-binding domain (DBD), the Hinge region (H), the ligand binding domain (LBD), and activation function domains (AF1, AF2) are shown. The numbering is based on an assumed length of 919 amino acids.
Figure 2
Figure 2. Mechanism of ligand-dependent gene transactivation by the androgen receptor. Testosterone (T) enters the prostate epithelial cell and is converted to dihydrotestosterone (DHT) by 5α-reductase. Binding of DHT to AR leads to dissociation of the AR-heat shock protein (HSP) complex, dimerization, and translocation to the nucleus. AR binds to specific DNA sequences termed androgen response elements (ARE) and recruits a series of co-activators to enhance transcription.
Figure 3
Figure 3. Crosstalk of growth factors with androgen receptor in prostate cancer cells. Major signaling pathways initiated by growth factor-AR crosstalk in the absence of or diminished levels of androgens, implicated in prostate cancer progression. Taken from Zhu and Kyprianou.
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