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IGFBP7: an oncosuppressor gene in thyroid carcinogenesis

Oncogene volume 29, pages 3835–3844 (2010)Cite this article

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Abstract

Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein involved in several cellular processes, including proliferation, senescence and apoptosis. Loss of IGFBP7 expression is a critical step in the development of human tumors, including melanoma and colon cancer. By microarray gene expression studies, we have detected downregulation of IGFBP7 gene expression in follicular and papillary thyroid tumors in comparison with normal thyroid tissue. Evaluation of publicly available PTC microarray gene expression data sets confirmed, in a consistent fraction of tumors, the downregulation of IGFBP7 transcript levels. The functional consequence of IGFBP7 downregulation was addressed in the PTC-derived NIM1 cell line in which IGFBP7 expression is repressed by promoter hypermethylation. Exposure to soluble IGFBP7 protein or restoration of IGFBP7 expression by complementary DNA transfection reduced growth rate, migration, anchorage-independent growth and tumorigenicity of NIM1 cells. We show that the effects of IGFBP7 are related to apoptosis. Our data suggest that loss of IGFBP7 expression has a functional role in thyroid carcinogenesis, and it may represent a possible basis for therapeutic strategies.

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Acknowledgements

The authors thank Mrs Sonia Pagliardini for technical assistance and Mrs Cristina Mazzadi for editing and secretarial help. This work was supported by AIRC grant N.4472, ACC and Ministry of Health.

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Authors and Affiliations

  1. Department of Experimental Oncology and Molecular Medicine, Molecular Mechanisms Unit, IRCCS Foundation—Istituto Nazionale dei Tumori, Milan, Italy

    M G Vizioli, C Miranda, M C Anania & A Greco

  2. Department of Experimental Oncology and Molecular Medicine, Human Tumors Immunobiology Unit, IRCCS Foundation—Istituto Nazionale dei Tumori, Milan, Italy

    M Sensi

  3. Department of Experimental Oncology and Molecular Medicine, Chemoprevention Unit, IRCCS Foundation—Istituto Nazionale dei Tumori, Milan, Italy

    L Cleris & F Formelli

  4. Department of Experimental Oncology and Molecular Medicine, Scientific Directorate, IRCCS Foundation—Istituto Nazionale dei Tumori, Milan, Italy

    M A Pierotti

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  1. M G Vizioli
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Correspondence to A Greco.

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Vizioli, M., Sensi, M., Miranda, C. et al. IGFBP7: an oncosuppressor gene in thyroid carcinogenesis. Oncogene 29, 3835–3844 (2010). https://doi.org/10.1038/onc.2010.136

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