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Dolichol-phosphate-mannose-3 (DPM3)/prostin-1 is a novel phospholipase C-γ regulated gene negatively associated with prostate tumor invasion

Oncogene volume 20, pages 2781–2790 (2001)Cite this article

Abstract

The most ominous development in tumor progression is the transition to an invasive and metastatic phenotype. Little is known, however, about the molecular alterations that cause a tumor to become invasive. In view of this, we have used microarray expression analysis to evaluate the expression profiles of a unique panel of human DU145 prostate cancer sublines that vary in their invasive potential. The three DU145 sublines expressed epidermal growth factor (EGF) receptors that differed in their ability to activate phospholipase C-γ (PLCγ). Three-way analyses yielded 11 genes out of 4608 genes screened that associated directly or inversely with invasive potential. The gene whose expression correlated most strongly with lack of invasion was identified as a potential invasion suppressor and called prostin-1. Pharmacological inhibition of PLCγ (U73122) confirmed that PLCγ signaling suppressed prostin-1 in that U73122 treatment caused induction of prostin-1 in PLCγ competent cells. The prostin-1 gene, conserved through phylogeny, is induced by androgen in LNCaP cells and encodes a 92 amino acid protein. The protein shares no extensive homologies with other known genes, yet was recently identified as a small stabilizer subunit of the dolichol-phosphate-mannose (DPM) synthase complex. That DPM3/prostin-1 might suppress tumor progression was supported by the finding that exogenous expression in COS cells leads to apoptosis. These findings support the use of model cell lines to identify putative tumor suppressors and promoters.

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Authors and Affiliations

  1. Division of Molecular Pharmacology, Hunstman Cancer Institute, University of Utah, Salt Lake City, 84112, Utah, UT, USA

    Elizabeth J Manos, Marianne L-H Kim & David A Jones

  2. Department of Pathology, University of Pittsburgh, and Pittsburgh VAMC, Pittsburgh, 15260, Pennsylvania, PA, USA

    Jareer Kassis & Alan Wells

  3. Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, Madison, 53706, Wisconsin, WI, USA

    Pei-Yun Chang

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  1. Elizabeth J Manos
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  2. Marianne L-H Kim
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Manos, E., Kim, MH., Kassis, J. et al. Dolichol-phosphate-mannose-3 (DPM3)/prostin-1 is a novel phospholipase C-γ regulated gene negatively associated with prostate tumor invasion. Oncogene 20, 2781–2790 (2001). https://doi.org/10.1038/sj.onc.1204379

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  • DOI: https://doi.org/10.1038/sj.onc.1204379

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