Lung-targeted expression of the c-Raf-1 kinase in transgenic mice exposes a novel oncogenic character of the wild-type protein

Eugen Kerkhoff, Lev Fedorov, Renate Siefken, Annette O. Walter, Thomas Papadopoulos, Ulf R. Rapp

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

The c-Raf-1 kinase is a downstream effector of Ras signaling. Both proteins are highly oncogenic when they are mutationally activated, but only the Ras GTPase is frequently mutated in naturally occurring tumors. Although the c-Raf-1 protein was found to be amplified in different lung cancer cell lines, overexpression of the wild-type c-Raf-1 protein was shown to be insufficient to transform cultured cells. Here we have addressed the question of whether overexpression of the wild-type c-Raf-1 kinase can induce lung cancer in mice. We show that lung-targeted expression of oncogenically activated or wild-type c-Raf-1 proteins induces morphologically indistinguishable lung adenomas in transgenic mice. Compared with mice transgenic for the activated c-Raf-1-BxB, tumor development is delayed and occurs at a lower incidence in wild-type c-Raf-1 transgenic mice. Our studies show that the c-Raf-1 expression level is a critical parameter in tumor development and should be analyzed in more detail to evaluate its potential in the induction of cancer.

Original languageEnglish (US)
Pages (from-to)185-190
Number of pages6
JournalCell Growth and Differentiation
Volume11
Issue number4
StatePublished - Apr 2000
Externally publishedYes

Fingerprint

Proto-Oncogene Proteins c-raf
Transgenic Mice
Lung
Proteins
Lung Neoplasms
Neoplasms
ras Proteins
Adenoma
Cultured Cells
Cell Line
Incidence

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Lung-targeted expression of the c-Raf-1 kinase in transgenic mice exposes a novel oncogenic character of the wild-type protein. / Kerkhoff, Eugen; Fedorov, Lev; Siefken, Renate; Walter, Annette O.; Papadopoulos, Thomas; Rapp, Ulf R.

In: Cell Growth and Differentiation, Vol. 11, No. 4, 04.2000, p. 185-190.

Research output: Contribution to journalArticle

Kerkhoff, Eugen ; Fedorov, Lev ; Siefken, Renate ; Walter, Annette O. ; Papadopoulos, Thomas ; Rapp, Ulf R. / Lung-targeted expression of the c-Raf-1 kinase in transgenic mice exposes a novel oncogenic character of the wild-type protein. In: Cell Growth and Differentiation. 2000 ; Vol. 11, No. 4. pp. 185-190.
@article{0dbd218d5d564bec8299b5ab8e1c622d,
title = "Lung-targeted expression of the c-Raf-1 kinase in transgenic mice exposes a novel oncogenic character of the wild-type protein",
abstract = "The c-Raf-1 kinase is a downstream effector of Ras signaling. Both proteins are highly oncogenic when they are mutationally activated, but only the Ras GTPase is frequently mutated in naturally occurring tumors. Although the c-Raf-1 protein was found to be amplified in different lung cancer cell lines, overexpression of the wild-type c-Raf-1 protein was shown to be insufficient to transform cultured cells. Here we have addressed the question of whether overexpression of the wild-type c-Raf-1 kinase can induce lung cancer in mice. We show that lung-targeted expression of oncogenically activated or wild-type c-Raf-1 proteins induces morphologically indistinguishable lung adenomas in transgenic mice. Compared with mice transgenic for the activated c-Raf-1-BxB, tumor development is delayed and occurs at a lower incidence in wild-type c-Raf-1 transgenic mice. Our studies show that the c-Raf-1 expression level is a critical parameter in tumor development and should be analyzed in more detail to evaluate its potential in the induction of cancer.",
author = "Eugen Kerkhoff and Lev Fedorov and Renate Siefken and Walter, {Annette O.} and Thomas Papadopoulos and Rapp, {Ulf R.}",
year = "2000",
month = "4",
language = "English (US)",
volume = "11",
pages = "185--190",
journal = "Molecular Cancer Research",
issn = "1541-7786",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

TY - JOUR

T1 - Lung-targeted expression of the c-Raf-1 kinase in transgenic mice exposes a novel oncogenic character of the wild-type protein

AU - Kerkhoff, Eugen

AU - Fedorov, Lev

AU - Siefken, Renate

AU - Walter, Annette O.

AU - Papadopoulos, Thomas

AU - Rapp, Ulf R.

PY - 2000/4

Y1 - 2000/4

N2 - The c-Raf-1 kinase is a downstream effector of Ras signaling. Both proteins are highly oncogenic when they are mutationally activated, but only the Ras GTPase is frequently mutated in naturally occurring tumors. Although the c-Raf-1 protein was found to be amplified in different lung cancer cell lines, overexpression of the wild-type c-Raf-1 protein was shown to be insufficient to transform cultured cells. Here we have addressed the question of whether overexpression of the wild-type c-Raf-1 kinase can induce lung cancer in mice. We show that lung-targeted expression of oncogenically activated or wild-type c-Raf-1 proteins induces morphologically indistinguishable lung adenomas in transgenic mice. Compared with mice transgenic for the activated c-Raf-1-BxB, tumor development is delayed and occurs at a lower incidence in wild-type c-Raf-1 transgenic mice. Our studies show that the c-Raf-1 expression level is a critical parameter in tumor development and should be analyzed in more detail to evaluate its potential in the induction of cancer.

AB - The c-Raf-1 kinase is a downstream effector of Ras signaling. Both proteins are highly oncogenic when they are mutationally activated, but only the Ras GTPase is frequently mutated in naturally occurring tumors. Although the c-Raf-1 protein was found to be amplified in different lung cancer cell lines, overexpression of the wild-type c-Raf-1 protein was shown to be insufficient to transform cultured cells. Here we have addressed the question of whether overexpression of the wild-type c-Raf-1 kinase can induce lung cancer in mice. We show that lung-targeted expression of oncogenically activated or wild-type c-Raf-1 proteins induces morphologically indistinguishable lung adenomas in transgenic mice. Compared with mice transgenic for the activated c-Raf-1-BxB, tumor development is delayed and occurs at a lower incidence in wild-type c-Raf-1 transgenic mice. Our studies show that the c-Raf-1 expression level is a critical parameter in tumor development and should be analyzed in more detail to evaluate its potential in the induction of cancer.

UR - http://www.scopus.com/inward/record.url?scp=0034036430&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034036430&partnerID=8YFLogxK

M3 - Article

C2 - 10775035

AN - SCOPUS:0034036430

VL - 11

SP - 185

EP - 190

JO - Molecular Cancer Research

JF - Molecular Cancer Research

SN - 1541-7786

IS - 4

ER -