NDLI: Exploiting the transcriptional specificity of the alpha-methylacyl-CoA racemase <i>AMACR</i> promoter for the molecular imaging of prostate cancer.

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Exploiting the transcriptional specificity of the alpha-methylacyl-CoA racemase AMACR promoter for the molecular imaging of prostate cancer.

Content Provider	Europe PMC
Author	Shapovalova, Mariya Davydova, Julia Henzler, Christine Daniel, Mark Dehm, Scott M. Warlick, Christopher A. LeBeau, Aaron M.
Copyright Year	2018
Abstract	The metabolic protein alpha-methylacyl-CoA racemase (AMACR) is significantly overexpressed in prostate cancer compared to the normal prostate and other non-malignant tissue. Though an attractive target, there are no reports in the literature on leveraging the expression of AMACR for the molecular imaging of prostate cancer. Here, we used a molecular-genetic imaging strategy to exploit the transcriptional specificity of the AMACR promoter for the in vivo detection of prostate cancer using the reporter gene luciferase. We performed a stepwise truncation of the promoter and identified a 565 base pair minimal promoter for AMACR that retained both high activity and specificity. Following identification of the minimal promoter for AMACR, we used an advanced two-step transcriptional amplification system to maximize the promoter output. We showed that our optimized AMACR promoter can drive expression of luciferase for molecular imaging in subcutaneous xenograft models of androgen receptor-positive and androgen receptor-negative prostate cancer using a non-replicative adenovirus for gene delivery. Our results provide evidence that the AMACR promoter can be exploited to drive the cancer-specific expression of reporter genes and potentially even be incorporated into conditionally replicative adenoviruses for oncolytic therapy and other applications.
Journal	Oncotarget
Volume Number	9
PubMed Central reference number	PMC6291171
Issue Number	94
PubMed reference number	30613352
e-ISSN	19492553
DOI	10.18632/oncotarget.26401
Language	English
Publisher	Impact Journals LLC
Publisher Date	2018-11-30
Access Restriction	Open
Rights License	This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. Copyright: © 2018 Shapovalova et al.
Subject Keyword	α-methylacyl-CoA racemase molecular imaging adenovirus prostate cancer
Content Type	Text
Resource Type	Article
Subject	Oncology

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