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Squamous cell carcinoma growth in mice and in culture is regulated by c-Jun and its control of matrix metalloproteinase-2 and -9 expression

Oncogene volume 25, pages 7260–7266 (2006)Cite this article

Abstract

Squamous cell carcinoma (SCC) is an invasive malignancy of epidermal keratinocytes. Surgical excision is currently the main treatment; however, this can cause scarring and disfigurement. There is accordingly, an acute need for alternative strategies to treat SCC. The transcription factor c-Jun is expressed in human SCC and another common form of invasive skin cancer, basal cell carcinoma together with the mitogenic marker-proliferating cell nuclear antigen. Here, we have employed DNAzymes (catalytic DNA molecules) targeting c-Jun (Dz13) to inhibit c-Jun expression in SCC cells. Dz13 inhibits SCC proliferation and suppresses solid SCC tumor growth and tumor angiogenesis in severe combined immunodeficient mice. We further demonstrate that Dz13 inhibits c-Jun, together with matrix metalloproteinase (MMP)-2 and MMP-9 expression in the tumors, consistent with DNAzyme inhibition of MMP-2 and MMP-9 gelatinolytic activity by zymography. Dz13 also suppressed the expression of vascular endothelial growth factor and fibroblast growth factor-2 in the tumors. These findings demonstrate that c-Jun regulates SCC growth and suggest that DNAzymes targeting this transcription factor may potentially be useful as inhibitors of cutaneous carcinoma.

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Acknowledgements

This work was supported by grants from the NSW Cancer Council and National Health and Medical Research Council of Australia. LMK is a Senior Principal Research Fellow of the NHMRC.

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Authors and Affiliations

  1. Centre for Vascular Research, University of New South Wales, Sydney, New South Wales, Australia

    G Zhang, X Luo & L M Khachigian

  2. Department of Haematology, Prince of Wales Hospital, Sydney, New South Wales, Australia

    G Zhang, X Luo & L M Khachigian

  3. Gribbles Pathology, Melbourne, Victoria, Australia

    E Sumithran

  4. Dermatology Research Laboratories, Royal Prince Alfred Hospital and University of Sydney, Sydney, New South Wales, Australia

    V S C Pua, R St C Barnetson & G M Halliday

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  1. G Zhang
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  2. X Luo
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Correspondence to L M Khachigian.

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Zhang, G., Luo, X., Sumithran, E. et al. Squamous cell carcinoma growth in mice and in culture is regulated by c-Jun and its control of matrix metalloproteinase-2 and -9 expression. Oncogene 25, 7260–7266 (2006). https://doi.org/10.1038/sj.onc.1209726

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