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.

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

TAULLI, Riccardo;ACCORNERO, Paolo;MOROTTI, Alessandro;BERSANI, Francesca;CREPALDI, Tiziana;CHIARLE, Roberto;NALDINI, Luigi;PONZETTO, Carola
2005-01-01

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.
2005
12(5)
456
463
TAULLI R; ACCORNERO P; FOLLENZI A; MANGANO T; MOROTTI A; SCUOPPO C; FORNI PE; BERSANI F; CREPALDI T; CHIARLE R; NALDINI L; PONZETTO C
File in questo prodotto:
File Dimensione Formato  
2005 ST Cancer Gene Therapy Taulli Accornero.pdf

Accesso riservato

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 355.52 kB
Formato Adobe PDF
355.52 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/41207
Citazioni
  • ???jsp.display-item.citation.pmc??? 14
  • Scopus 34
  • ???jsp.display-item.citation.isi??? 31
social impact