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

Riccardo Taulli, Paolo Accornero, Antonia Follenzi, Tony Mangano, Alessandro Morotti, Claudio Scuoppo, Paolo E. Forni, Francesca Bersani, Tiziana Crepaldi, Roberto Chiarle, Luigi Naldini, Carola Ponzetto

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)456-463
Number of pages8
JournalCancer Gene Therapy
Volume12
Issue number5
DOIs
Publication statusPublished - May 2005

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Keywords

  • Gastric cancer
  • Lentiviral vector
  • Novel cancer therapies
  • ShRNA
  • Tpr-Met

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Taulli, R., Accornero, P., Follenzi, A., Mangano, T., Morotti, A., Scuoppo, C., Forni, P. E., Bersani, F., Crepaldi, T., Chiarle, R., Naldini, L., & Ponzetto, C. (2005). RNAi technology and lentiviral delivery as a powerful tool to suppress Tpr-Met-mediated tumorigenesis. Cancer Gene Therapy, 12(5), 456-463. https://doi.org/10.1038/sj.cgt.7700815