Abstract

Prostate cancer remains the most common malignancy among men in United States, and there is no remedy currently available for the advanced stage hormone-refractory cancer. This is partly due to the incomplete understanding of androgen-regulated proteins and their encoded functions. Whole-cell proteomes of androgen-starved and androgen-treated LNCaP cells were analyzed by semi-quantitative MudPIT ESI- ion trap MS/MS and quantitative iTRAQ MALDI- TOF MS/MS platforms, with identification of more than 1300 high-confidence proteins. An enrichment-based pathway mapping of the androgen-regulated proteomic data sets revealed a significant dysregulation of aminoacyl tRNA synthetases, indicating an increase in protein biosynthesis- a hallmark during prostate cancer progression. This observation is supported by immunoblot and transcript data from LNCaP cells, and prostate cancer tissue. Thus, data derived from multiple proteomics platforms and transcript data coupled with informatics analysis provides a deeper insight into the functional consequences of androgen action in prostate cancer.

Highlights

  • Cancer of the prostate (PCa) is the most commonly diagnosed cancer among men in the United States, with an estimated 200,000 new cases and 29,000 deaths for 2008 [1]

  • From the many molecular concepts, including the androgen-regulated and prostate cancer concepts that were enriched by our androgen up-regulated data set, the concept describing elevated aminoacyl tRNA synthetases was selected for further examination

  • Using transcriptomic profiling and chromatin immunoprecipitation, we showed that androgen drives the expression of aminoacyl tRNA synthetases (aaRS) at the transcript level

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Summary

Introduction

Cancer of the prostate (PCa) is the most commonly diagnosed cancer among men in the United States, with an estimated 200,000 new cases and 29,000 deaths for 2008 [1]. Multiple groups have interrogated androgen-regulated changes at the transcriptome and proteome levels using gene expression arrays and mass spectrometry, respectively [4,5,6,7,8,9,10], there is still a lack of considerable understanding on the functional consequence of the hormone action during prostate cancer development. This deficiency is a reflection of the sparseness in the proteomic data; due to the limitations of proteomic technologies, the total number of proteins identified and quantified in a single study is modest. There are technical challenges from such under-representation of proteins and in assessing the statistical significance of differences in protein expression

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