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

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

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

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

Division of Molecular Medicine and Gene Therapy

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1360-1366
Journal	Cell Cycle
Volume	6
Issue number	11
Publication status	Published - 2007

Subject classification (UKÄ)

Cell Biology

Free keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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http://www.landesbioscience.com/journals/cc/article/4268

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@article{60b77a3279c347dba5860ae858c34100,

title = "TGF-beta receptor I conditional knockout mice develop spontaneous squamous cell carcinoma",

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.",

keywords = "TGF-beta, Cre-lox P system, IL-13, TGF-beta receptor I, squamous cell carcinoma, cytotoxin, head and neck cancer",

author = "Yasuyuki Honjo and Yansong Bian and Koji Kawakami and Alfredo Molinolo and Glenn Longenecker and Ramanamurthy Boppana and Jonas Larsson and Stefan Karlsson and Gutkind, {J. Silvio} and Puri, {Raj K.} and Kulkarni, {Ashok B.}",

year = "2007",

language = "English",

volume = "6",

pages = "1360--1366",

journal = "Cell Cycle",

issn = "1551-4005",

publisher = "Landes Bioscience",

number = "11",

}

TY - JOUR

T1 - TGF-beta receptor I conditional knockout mice develop spontaneous squamous cell carcinoma

AU - Honjo, Yasuyuki

AU - Bian, Yansong

AU - Kawakami, Koji

AU - Molinolo, Alfredo

AU - Longenecker, Glenn

AU - Boppana, Ramanamurthy

AU - Larsson, Jonas

AU - Karlsson, Stefan

AU - Gutkind, J. Silvio

AU - Puri, Raj K.

AU - Kulkarni, Ashok B.

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - TGF-beta

KW - Cre-lox P system

KW - IL-13

KW - TGF-beta receptor I

KW - squamous cell carcinoma

KW - cytotoxin

KW - head and neck cancer

M3 - Article

SN - 1551-4005

VL - 6

SP - 1360

EP - 1366

JO - Cell Cycle

JF - Cell Cycle

IS - 11

ER -

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

Abstract

Subject classification (UKÄ)

Free keywords

UN SDGs

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