TGF-beta receptor I conditional knockout mice develop spontaneous squamous cell carcinoma

Summary, in English

We generated a mouse model with a conditional deletion of TGF-beta signaling in the neurons by crossing TGF-beta receptor I (T beta RI) floxed mice with neurofilament-H (NF-H) Cre mice. 35% of F1 conditional knockout (COKO) mice developed spontaneous squamous cell carcinomas (SCCs) in periorbital and/ or perianal regions. Transplantation of these tumors into athymic nude mice resulted in 62% tumorigenicity. To determine whether evasion of the immune response plays any role in this tumorigenesis, we analyzed the expression levels of receptors for interleukin-13 (mIL-13R), a key negative regulator of tumor immunosurveillance, and found that 33% of COKO tumors expressed the IL-13R alpha 2 chain. Primary cultures of the SCCs expressing IL-13R alpha 2 were sensitive to the cytotoxic effect of IL-13R-directed cytotoxin treatment. This is the first demonstration that loss of T beta RI can lead to spontaneous tumor formation. These mice can serve as a unique mouse model of SCC to evaluate the tumorigenicity and effect of anti-cancer therapeutics.

• Författare: Yasuyuki Honjo; Yansong Bian; Koji Kawakami; Alfredo Molinolo; Glenn Longenecker; Ramanamurthy Boppana; Jonas Larsson; Stefan Karlsson; J. Silvio Gutkind; Raj K. Puri; Ashok B. Kulkarni
• Avdelning/ar: Avdelningen för molekylärmedicin och genterapi
• Publiceringsår: 2007
• Språk: Engelska
• Sidor: 1360-1366
• Publikation/Tidskrift/Serie: Cell Cycle
• Volym: 6
• Issue: 11
• Länkar: http://www.landesbioscience.com/journals/cc/article/4268
• Dokumenttyp: Artikel i tidskrift
• Förlag: Landes Bioscience
• Ämne: Cell Biology
• Nyckelord: TGF-beta; Cre-lox P system; IL-13; TGF-beta receptor I; squamous cell carcinoma; cytotoxin; head and neck cancer
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1551-4005