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

Honjo, Yasuyuki; Bian, Yansong; Kawakami, Koji; Molinolo, Alfredo; Longenecker, Glenn; Boppana, Ramanamurthy; Larsson, Jonas LU ; Karlsson, Stefan LU ; Gutkind, J. Silvio and Puri, Raj K., et al. (2007) In Cell Cycle 6(11). p.1360-1366
Abstract
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... (More)
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. (Less)
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Contribution to journal
publication status
published
subject
keywords
TGF-beta, Cre-lox P system, IL-13, TGF-beta receptor I, squamous cell carcinoma, cytotoxin, head and neck cancer
in
Cell Cycle
volume
6
issue
11
pages
1360 - 1366
publisher
Landes Bioscience
external identifiers
  • wos:000248081700016
ISSN
1551-4005
language
English
LU publication?
yes
id
60b77a32-79c3-47db-a586-0ae858c34100 (old id 645890)
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http://www.landesbioscience.com/journals/cc/article/4268
date added to LUP
2007-12-12 16:02:16
date last changed
2016-04-15 19:25:22
@article{60b77a32-79c3-47db-a586-0ae858c34100,
  abstract     = {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.},
  author       = {Honjo, Yasuyuki and Bian, Yansong and Kawakami, Koji and Molinolo, Alfredo and Longenecker, Glenn and Boppana, Ramanamurthy and Larsson, Jonas and Karlsson, Stefan and Gutkind, J. Silvio and Puri, Raj K. and Kulkarni, Ashok B.},
  issn         = {1551-4005},
  keyword      = {TGF-beta,Cre-lox P system,IL-13,TGF-beta receptor I,squamous cell carcinoma,cytotoxin,head and neck cancer},
  language     = {eng},
  number       = {11},
  pages        = {1360--1366},
  publisher    = {Landes Bioscience},
  series       = {Cell Cycle},
  title        = {TGF-beta receptor I conditional knockout mice develop spontaneous squamous cell carcinoma},
  volume       = {6},
  year         = {2007},
}