title: RNAi technology and lentiviral delivery as a powerful tool to suppress Tpr-Met-mediated tumorigenesis.
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.
authors.affiliation: Center for Experimental Research and Medical Studies (CERMS), Molinette Hospital, Turin, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Taulli
authors.forename: Paolo
authors.initials: P
authors.lastname: Accornero
authors.forename: Antonia
authors.initials: A
authors.lastname: Follenzi
authors.forename: Tony
authors.initials: T
authors.lastname: Mangano
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morotti
authors.forename: Claudio
authors.initials: C
authors.lastname: Scuoppo
authors.forename: Paolo E
authors.initials: PE
authors.lastname: Forni
authors.forename: Francesca
authors.initials: F
authors.lastname: Bersani
authors.forename: Tiziana
authors.initials: T
authors.lastname: Crepaldi
authors.forename: Roberto
authors.initials: R
authors.lastname: Chiarle
authors.forename: Luigi
authors.initials: L
authors.lastname: Naldini
authors.forename: Carola
authors.initials: C
authors.lastname: Ponzetto
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D009374:Neoplasms, Experimental / Q000209:etiology / Q000628:therapy*; D015514:Oncogene Proteins, Fusion / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: D015514:Oncogene Proteins, Fusion; D034741:RNA, Small Interfering