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High expression of shMDG1 gene is associated with low metastatic potential of tumor cells

Oncogene volume 25, pages 317–322 (2006)Cite this article

Abstract

Metastasis is the primary cause of mortality associated with cancer. Molecular mechanisms leading to metastatic spread are poorly studied. To get a better understanding of this process, we compared the gene expression pattern of two isogenic cell lines, HET-SR and HET-SR1 (Rous Sarcoma Virus-transformed embryo hamster fibroblasts) with different metastatic activity using the differential display technique. A novel cDNA of hamster gene shMDG1 (Syrian hamster homologue of microvascular differentiation gene 1), which had 94% homology with rat MDG1 gene, was identified. Expression of shMDG1 was increased in low metastatic HET-SR cell line in comparison to high metastatic HET-SR1. Sequence analysis of the ORF of shMDG1 gene showed that it belongs to the DnaJ/heat-shock proteins of 40 kDa (HSP40) chaperones family, considered to function as a cochaperone of HSP70 family. In order to confirm involvement of shMDG1 in metastasis, we injected parental and shMDG1 overexpressed cells into animals. We showed that overexpression of the shMDG1 gene significantly diminished the metastatic activity of both HET-SR and HET-SR1 cells. The shMDG1-induced repression of metastasis was not connected with alterations in cell proliferation and motility in vitro, but correlated well with a decrease in content of the Asn-linked β1–6 branched oligosaccharides on cell surface.

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Acknowledgements

We are grateful to Dr I Zborovskaya, Dr A Gasparian, Dr N Lazarevich and Dr B Kopnin (Cancer Research Center, Moscow, Russia) for the fruitful discussion, and A Komelkov for excellent technical assistance. This work was funded by the Russian National Fund for Basic Research (05-04-48871).

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Authors and Affiliations

  1. Viral and Cellular Oncogenes Lab,

    N Isachenko, N Dyakova, V Aushev, T Chepurnych & A Tatosyan

  2. oratory, Cancer Research Center, Institute of Carcinogenesis, Moscow, Russia

    N Isachenko, N Dyakova, V Aushev, T Chepurnych & A Tatosyan

  3. Department of Molecular Genetics, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, USA

    K Gurova

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  1. N Isachenko
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  2. N Dyakova
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  3. V Aushev
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  4. T Chepurnych
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  5. K Gurova
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  6. A Tatosyan
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Correspondence to N Isachenko.

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Isachenko, N., Dyakova, N., Aushev, V. et al. High expression of shMDG1 gene is associated with low metastatic potential of tumor cells. Oncogene 25, 317–322 (2006). https://doi.org/10.1038/sj.onc.1209022

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