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Re-expression of TSLC1 in a non-small-cell lung cancer cell line induces apoptosis and inhibits tumor growth

Oncogene volume 23, pages 5632–5642 (2004)Cite this article

Abstract

The TSLC1 tumor-suppressor gene is silenced in a number of human cancer tissues and cell lines, including lung, prostate, liver, stomach, pancreatic, and breast cancers. Expression of TSLC1 in a non-small-cell lung cancer (NSCLC) cell line A549 suppresses tumorigenicity in nude mice. However, the molecular mechanism of TSLC1 action is not yet elucidated. In the present study, we show that the expression of TSLC1 from a recombinant adenovirus vector (Ad-TSLC1) inhibited cell proliferation and induced apoptosis in the NSCLC cell line A549. We also demonstrated that subcutaneous tumor growth in nude mice induced by A549 cells was suppressed to the extent of 70–80% by intratumoral injection of Ad-TSLC1. Re-expression of TSLC1 also resulted in activation of the apoptotic protease caspase-3, accompanied by the cleavage of its substrate poly (ADP-ribose) polymerase (PARP). The antiproliferative and pro-apoptotic activity of TSLC1 required the presence of the FERM-binding and PDZ-interacting motifs located in the cytoplasmic domain. Our results demonstrate the pro-apoptotic and oncosuppressive activity of TSLC1 protein, and suggest the potential of TSLC1 for gene therapy.

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Acknowledgements

We thank G Singh, J Hassell, DW Andrews, M Annis, J Knez, N McFarlaine, and J Rudy for their help and J Paul for manuscript preparation. This study was supported by the National Cancer Institute of Canada.

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Authors and Affiliations

  1. Department of Biochemistry, McMaster University, 1200 Main Street West, Hamilton, L8N 3Z5, ON, Canada

    Xinliang Mao, Ray Truant & Hara P Ghosh

  2. Hamilton Regional Cancer Center, 699 Concession St., Hamilton, L8V 5C2, ON, Canada

    Eric Seidlitz

  3. Department of Pathology and Molecular Medicine, McMaster University, 1200 Main Street West, Hamilton, L8N 3Z5, ON, Canada

    Mary Hitt

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  1. Xinliang Mao
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Correspondence to Hara P Ghosh.

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Mao, X., Seidlitz, E., Truant, R. et al. Re-expression of TSLC1 in a non-small-cell lung cancer cell line induces apoptosis and inhibits tumor growth. Oncogene 23, 5632–5642 (2004). https://doi.org/10.1038/sj.onc.1207756

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