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Insulin-like growth factor binding protein-6 activates programmed cell death in non-small cell lung cancer cells

Oncogene volume 19, pages 4432–4436 (2000)Cite this article

Abstract

Insulin-like growth factor binding proteins (IGFBPs) are secreted into the extra-cellular matrix and inhibit cell growth through IGF-dependent and -independent mechanisms. In this study, we investigated the role of IGFBP-6, a relatively unexplored member of the IGFBP family, in the proliferation of non-small cell lung cancer (NSCLC) cells. Infection of NSCLC cell lines in vitro with an adenovirus expressing human IGFBP-6 under the control of a CMV promoter (Ad5CMV-BP6) reduced NSCLC cell number through activation of programmed cell death, as shown by cell staining with Hoechst 33342 or DNA end-labeling with bromodeoxyuridine triphosphate. The growth regulatory effect of IGFBP-6 was investigated in vivo by intratumoral injection of Ad5CMV-BP6 in NSCLC xenografts established in nu/nu mice. A single injection of Ad5CMV-BP6 reduced the size of NSCLC xenografts by 45%. These findings indicate that IGFBP-6 is a potent inducer of programmed cell death in cancer cells and support investigations into IGFBP-6 as a potential target in cancer therapeutics.

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Acknowledgements

Supported in part by NIH Grant R29 CA67353 and P50 CA70907 (Lung Cancer SPORE).

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Authors and Affiliations

  1. Department of Thoracic/Head and Neck Medical Oncology, University of Texas-MD Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    Naoko Sueoka, Ho-Young Lee, Waun Ki Hong & Jonathan M Kurie

  2. Department of Genitourinary Medical Oncology, University of Texas-MD Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    Sandra Wiehle & Richard J Cristiano

  3. Department of Thoracic and Cardiovascular Surgery, University of Texas-MD Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    BingLiang Fang, Lin Ji & Jack A Roth

  4. Department of Pediatrics, University of California at Los Angeles, Los Angeles, 90095, California, CA, USA

    Pinchas Cohen

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  1. Naoko Sueoka
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  2. Ho-Young Lee
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Sueoka, N., Lee, HY., Wiehle, S. et al. Insulin-like growth factor binding protein-6 activates programmed cell death in non-small cell lung cancer cells. Oncogene 19, 4432–4436 (2000). https://doi.org/10.1038/sj.onc.1203813

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