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Inhibition of prostate cancer growth and metastasis using small interference RNA specific for minichromosome complex maintenance component 7

Cancer Gene Therapy volume 17, pages 694–699 (2010)Cite this article

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Abstract

Minichromosome complex maintenance component 7 (MCM7) is a critical component of DNA replication licensing. Amplification and overexpression of MCM7 leads to high rate of prostate cancer metastasis. Recent studies indicate that MCM7 genome encodes a putative ‘super-oncogene’ cluster including MCM7 oncogene and a miRNA cluster that knocks down the expression of several critical tumor-suppressor genes. In this study, we constructed a vector that constitutively expresses small interference RNA (siRNA) specific for MCM7. Introduction of this vector into prostate cancer cell lines PC3 or Du145 decreases the expression of MCM7 by 80%. The vector inhibits DNA synthesis and generates growth arrest of these cancer cells. Severe combined immunodeficient mice were xenografted PC3 or Du145 tumors, and subsequently treated with this vector through tail vein injection with polyethylenimine. The animals had dramatically smaller tumor volume, less metastasis and better survival rate in comparison with the controls. As a result, intervention of MCM7 expression using siRNA approach may hold the promise for treating androgen refractory prostate cancer.

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Acknowledgements

This work was supported by grants from National Cancer Institute (RO1 CA098249 to JHL), Department of Defense (W81 XWH-09-1-0376 to JHL), and American Cancer Society (RSG-08-137-01-CNE to YPY).

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  1. Department of Pathology and Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Y-K Shi, Y P Yu, G C Tseng & J-H Luo

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  1. Y-K Shi
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  2. Y P Yu
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Correspondence to J-H Luo.

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Shi, YK., Yu, Y., Tseng, G. et al. Inhibition of prostate cancer growth and metastasis using small interference RNA specific for minichromosome complex maintenance component 7. Cancer Gene Ther 17, 694–699 (2010). https://doi.org/10.1038/cgt.2010.25

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