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Novel gene C17orf37 in 17q12 amplicon promotes migration and invasion of prostate cancer cells

Oncogene volume 28, pages 2860–2872 (2009)Cite this article

Abstract

C17orf37/MGC14832, a novel gene located on human chromosome 17q12 in the ERBB2 amplicon, is abundantly expressed in breast cancer. C17orf37 expression has been reported to positively correlate with grade and stage of cancer progression; however the functional significance of C17orf37 overexpression in cancer biology is not known. Here, we show that C17orf37 is highly expressed in prostate cancer cell lines and tumors, compared to minimal expression in normal prostate cells and tissues. Cellular localization studies by confocal and total internal reflection fluorescence microscopy revealed predominant expression of C17orf37 in the cytosol with intense staining in the membrane of prostate cancer cells. RNA-interference-mediated downregulation of C17orf37 resulted in decreased migration and invasion of DU-145 prostate cancer cells, and suppressed the DNA-binding activity of nuclear factor-κB (NF-κB) transcription factor resulting in reduced expression of downstream target genes matrix metalloproteinase 9, urokinase plasminogen activator and vascular endothelial growth factor. Phosphorylation of PKB/Akt was also reduced upon C17orf37 downregulation, suggesting C17orf37 acts as a signaling molecule that increases invasive potential of prostate cancer cells by NF-κB-mediated downstream target genes. Our data strongly suggest C17orf37 overexpression in prostate cancer functionally enhances migration and invasion of tumor cells, and is an important target for cancer therapy.

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Acknowledgements

We thank Dr Linda Cunnighum (UNTHSC) for assistance with immunohistochemistry and Dr Kapil Mehta (MD Anderson Cancer Center, TX) for help with migration assays. The present work is supported by grant nos. CA109593 and MD 001633 (JKV) from NIH and DOD PCRP Training Award PC081282 (SD). UNMC/Eppley Cancer Center Tumor Bank was supported by an NCI Cancer Center Support Grant P30 CA36727 and Nebraska Department of Health Institutional LB595 Grant for Cancer and Smoking Disease Research.

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Authors and Affiliations

  1. Department of Biomedical Sciences and Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX, USA

    S Dasgupta & J K Vishwanatha

  2. Department of Pathology, Harris Methodist Fort Worth Hospital, Fort Worth, TX, USA

    L M Wasson

  3. Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX, USA

    N Rauniyar, L Prokai, J Borejdo & J K Vishwanatha

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  1. S Dasgupta
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  2. L M Wasson
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Correspondence to J K Vishwanatha.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Dasgupta, S., Wasson, L., Rauniyar, N. et al. Novel gene C17orf37 in 17q12 amplicon promotes migration and invasion of prostate cancer cells. Oncogene 28, 2860–2872 (2009). https://doi.org/10.1038/onc.2009.145

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