| Literature DB >> 17534148 |
Yasuyuki Honjo1, Yansong Bian, Koji Kawakami, Alfredo Molinolo, Glenn Longenecker, Ramanamurthy Boppana, Jonas Larsson, Stefan Karlsson, J Silvio Gutkind, Raj K Puri, Ashok B Kulkarni.
Abstract
We generated a mouse model with a conditional deletion of TGF-beta signaling in the neurons by crossing TGF-beta receptor I (TbetaRI) 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 alpha2 chain. Primary cultures of the SCCs expressing IL-13R alpha2 were sensitive to the cytotoxic effect of IL-13R-directed cytotoxin treatment. This is the first demonstration that loss of TbetaRI 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.Entities:
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Year: 2007 PMID： 17534148 DOI： 10.4161/cc.6.11.4268
Source DB: PubMed Journal: Cell Cycle ISSN： 1551-4005 Impact factor: 4.534