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Melanoma Differentiation Associated Gene-7 (mda-7): A Novel Anti-Tumor Gene for Cancer Gene Therapy

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Abstract

Background

The mda-7 gene (melanoma differentiation associated gene-7) is a novel tumor suppressor gene. The anti-proliferative activity of MDA-7 has been previously reported. In this report, we analyze the antitumor efficacy of Ad-mda7 in a broad spectrum of cancer lines.

Materials and Methods

Ad-mda7-transduced cancer or normal cell lines were assayed for cell proliferation (tritiated thymidine incorporation assay, Alamar blue assay, and trypan-blue exclusion assay), apoptosis (TUNEL, and Annexin V staining visualized by fluorescent microscopy or FACs analysis), and cell cycle regulation (Propidium Iodide staining and FACs analysis).

Results

Ad-mda7 treatment of tumor cells resulted in growth inhibition and apoptosis in a temporal and dose-dependent manner. The anti-tumor effects were independent of the genomic status of p53, RB, p16, ras, bax, and caspase 3 in these cells. In addition, normal cell lines did not show inhibition of proliferation or apoptotic response to Ad-mda7. Moreover, Ad-mda7-transduced cancer cells secreted a soluble form of MDA-7 protein. Thus, Ad-mda7 may represent a novel gene-therapeutic agent for the treatment of a variety of cancers.

Conclusions

The potent and selective killing activity of Ad-mda7 in cancer cells but not in normal cells makes this vector a potential candidate for cancer gene therapy.

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Acknowledgements

This research was supported by Introgen Therapeutics Inc., Houston, TX. and NCI grant R43 CA86587 to SC.

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Authors and Affiliations

  1. Introgen Therapeutics Inc., 2250 Holcombe Blvd, Houston, TX, 77030, USA

    Abner M. Mhashilkar, Robert D. Schrock, Mustafa Hindi, Jennifer Liao, Kerry Sieger, Famourou Kourouma, X. Helena Zou-Yang, Eric Onishi, Oksana Takh &  Sunil Chada

  2. Corixa Inc., Seattle, WA, USA

    Thomas S. Vedvick & Gary Fanger

  3. Applied Development Laboratory, Imperial Cancer Research Fund, London, UK

    Lorna Stewart, Graham J. Watson & David Snary

  4. Departments of Neurosurgery, Pathology and Urology, Columbia University, College of Physicians and Surgeons, New York, NY, USA

    Paul B. Fisher

  5. Department of Thoracic and Cardiovascular Surgery, M.D. Anderson Cancer Center, Houston, TX, 77030, USA

    Tomoyuki Saeki, Jack A. Roth & Rajagopal Ramesh

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  1. Abner M. Mhashilkar
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  2. Robert D. Schrock
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  19. Sunil Chada
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Corresponding author

Correspondence to Sunil Chada.

Additional information

Contributed by A. B. Pardee.

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Mhashilkar, A.M., Schrock, R.D., Hindi, M. et al. Melanoma Differentiation Associated Gene-7 (mda-7): A Novel Anti-Tumor Gene for Cancer Gene Therapy. Mol Med 7, 271–282 (2001). https://doi.org/10.1007/BF03401847

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