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Transcriptional and post-transcriptional regulation of Sprouty1, a receptor tyrosine kinase inhibitor in prostate cancer

Prostate Cancer and Prostatic Diseases volume 14, pages 279–285 (2011)Cite this article

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An Erratum to this article was published on 12 November 2013

Abstract

Sprouty1 (Spry1) is a negative regulator of fibroblast growth factor signaling with a potential tumor suppressor function in prostate cancer (PCa). Spry1 is downregulated in human PCa, and Spry1 expression can markedly inhibit PCa proliferation in vitro. We have reported DNA methylation as a mechanism for controlling Spry1 expression. However, promoter methylation does not seem to explain gene silencing in all PCa cases studied to suggest other mechanisms of gene inactivation, such as alterations in trans-acting factors and/or post-transcriptional activity may be responsible for the decreased expression in those cases. Binding sites for Wilm's tumor (WT1) transcription factors EGR1, EGR3 and WTE are highly conserved between the mouse and human Spry1 promoter regions, suggesting an evolutionary conserved mechanism(s) involving WT1 and EGR in Spry1 regulation. Spry1 mRNA contains multiple microRNA (miRNA) binding sites in its 3′UTR region suggesting post-transcriptional control. We demonstrate that Spry1 is a target for miR-21-mediated gene silencing. miRNA-based therapeutic approaches to treat cancer are emerging. Spry1 is highly regulated by miRNAs and could potentially be an excellent candidate for such approaches.

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Acknowledgements

This work was supported by a grant from the Department of Defense Prostate Cancer Research Program New Investigator Award (PC040326) to BK-A. MI received support from the Department of Veterans Affairs Merit Review program and from the National Cancer Institute to the Baylor prostate cancer SPORE program (P50CA058204).

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Authors and Affiliations

  1. Howard University Cancer Center, Washington, DC, USA

    M Darimipourain, S Wang & B Kwabi-Addo

  2. Department of Pathology, Baylor College of Medicine, Houston, TX, USA

    M Ittmann

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  1. M Darimipourain
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  2. S Wang
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  4. B Kwabi-Addo
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Correspondence to B Kwabi-Addo.

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Darimipourain, M., Wang, S., Ittmann, M. et al. Transcriptional and post-transcriptional regulation of Sprouty1, a receptor tyrosine kinase inhibitor in prostate cancer. Prostate Cancer Prostatic Dis 14, 279–285 (2011). https://doi.org/10.1038/pcan.2011.33

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