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

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Author

  • 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
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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.

Publishing year

2007

Language

English

Pages

1360-1366

Publication/Series

Cell Cycle

Volume

6

Issue

11

Document type

Journal article

Publisher

Landes Bioscience

Topic

  • Cell Biology

Keywords

  • TGF-beta
  • Cre-lox P system
  • IL-13
  • TGF-beta receptor I
  • squamous cell carcinoma
  • cytotoxin
  • head and neck cancer

Status

Published

ISBN/ISSN/Other

  • ISSN: 1551-4005