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RNAi technology and lentiviral delivery as a powerful tool to suppress Tpr-Met-mediated tumorigenesis

Cancer Gene Therapy volume 12, pages 456–463 (2005)Cite this article

Abstract

Tpr-Met, the oncogenic counterpart of the Met receptor, has been detected in gastric cancers, as well as in precursor lesions and in the adjacent normal gastric mucosa. This has prompted the suggestion that Tpr-Met may predispose to the development of gastric tumors. Given the sequence specificity of RNA interference, oncogenes activated by point mutation or rearrangements can be targeted while spearing the product of the wild-type allele. In this work, we report specific suppression of Tpr-Met expression and inhibition of Tpr-Met-mediated transformation and tumorigenesis by means of a short interfering RNA (siRNA) directed toward the Tpr-Met junction (anti-TM2). When delivered by a lentiviral vector, anti-TM2 siRNA was effective also in mouse embryonal fibroblasts or epithelial cells expressing high levels of Tpr-Met. Our results suggest that lentiviral-mediated delivery of anti-TM2 siRNA may be developed into a powerful tool to treat Tpr-Met-positive cancers.

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Acknowledgements

We are grateful to Roberto Piva, Andrea Manazza and Chiara Ambrogio for technical help. This work was supported by funds from the Italian Association for Cancer Research (AIRC, CP), the Oncology Project Compagnia di San Paolo/FIRMS (CeRMS) and PRIN 2003 (CP, LN). Paolo Accornero is a FIRC fellow. The continuing support of the Compagnia di San Paolo and Fondazione CRT to C Ponzetto's laboratory is gratefully acknowledged.

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Author notes

  1. Antonia Follenzi

    Present address: Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Ullmann 625, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

  2. Luigi Naldini

    Present address: HSR-Telethon Institute for Gene Therapy and Vita Salute University, H San Raffaele Scientific Institute, Milan, Italy

  3. Riccardo Taulli and Paolo Accornero: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Experimental Research and Medical Studies (CERMS), Molinette Hospital, Turin, Italy

    Riccardo Taulli, Paolo Accornero, Tony Mangano, Alessandro Morotti, Claudio Scuoppo, Paolo E Forni, Francesca Bersani, Tiziana Crepaldi, Roberto Chiarle & Carola Ponzetto

  2. Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, C.so Massimo d'Azeglio 52, 10126, Turin, Italy

    Riccardo Taulli, Paolo Accornero, Tony Mangano, Alessandro Morotti, Claudio Scuoppo, Paolo E Forni, Francesca Bersani, Tiziana Crepaldi & Carola Ponzetto

  3. Laboratory of Gene Transfer and Therapy, Institute for Cancer Research and Treatment (IRCC), University of Torino, Turin, Italy

    Antonia Follenzi & Luigi Naldini

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  1. Riccardo Taulli
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Correspondence to Carola Ponzetto.

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Taulli, R., Accornero, P., Follenzi, A. et al. RNAi technology and lentiviral delivery as a powerful tool to suppress Tpr-Met-mediated tumorigenesis. Cancer Gene Ther 12, 456–463 (2005). https://doi.org/10.1038/sj.cgt.7700815

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