Abstract
Androgen exerts its functions by binding with an androgen receptor (AR). It can activate many signaling pathways that are important to the progression of castration-resistant prostate cancer (CRPC). Here, we characterized the rapid proteomic changes seen at 5, 15, 30, and 60 min after the androgen treatment of VCaP cells via the tandem mass tag (TMT) labeling strategy. A total of 5529 proteins were successfully identified and quantified. Dynamic time profiling of protein expression patterns allowed us to identify five protein clusters involved in various stages of androgen-initiated signal transmission and processing. More details of protein functions and localization patterns, and our elucidation of an AR-interacting protein network, were obtained. Finally, we validated the expression level of AR-regulated proteins known to be significantly regulated in CRPC patients using the mouse xenograft model and patient samples. Our work offers a systematic analysis of the rapid proteomic changes induced by androgen and provides a global view of the molecular mechanisms underlying CRPC progression.
Highlights
IntroductionProstate cancer is the second leading cause of male cancer, and it is one of the most common causes of cancer death (after lung cancer) in the United States [1]
Prostate cancer is the second leading cause of male cancer, and it is one of the most common causes of cancer death in the United States [1]
Most patients treated with androgen-deprivation therapies experience a disease recurrence that is known as castration-resistant prostate cancer (CRPC)
Summary
Prostate cancer is the second leading cause of male cancer, and it is one of the most common causes of cancer death (after lung cancer) in the United States [1]. The development of prostate cancer is induced by androgens; androgen-deprivation therapies, such as medical or surgical castration, are used to decrease the physiological androgen level in more than 30% of patients diagnosed with prostate cancer [2,3]. Most patients treated with androgen-deprivation therapies experience a disease recurrence that is known as castration-resistant prostate cancer (CRPC). One mechanism responsible for the development of CRPC is the acquisition of the metabolic capability to convert steroid precursors to dihydrotestosterone (DHT), which leads to the activation of androgen receptor (AR). AR, which is a member of the nuclear receptor superfamily, contributes to the development of both normal prostate and prostate cancer.
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