Expression of Transforming Growth Factor Alpha and Epidermal Growth Factor Receptor in Rat Lung Neoplasms Induced by Plutonium-239

Ninety-two rat lung proliferative lesions and neoplasms induced by inhaled 239 PuO2 were evaluated for aberrant expression of transforming growth factor alpha (TGF-α) and epidermal growth factor receptor (EGFR). Expression of TGF-α protein, measured by immunohistochemistry, was higher in 94% of the...

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Veröffentlicht in:Radiation Research 1994-11, Vol.140 (2), p.191-198
Hauptverfasser: Stegelmeier, Bryan L., Gillett, Nancy A., Hahn, Fletcher F., Rebar, Alan H., Kelly, Gregory
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container_issue 2
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container_title Radiation Research
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creator Stegelmeier, Bryan L.
Gillett, Nancy A.
Hahn, Fletcher F.
Rebar, Alan H.
Kelly, Gregory
description Ninety-two rat lung proliferative lesions and neoplasms induced by inhaled 239 PuO2 were evaluated for aberrant expression of transforming growth factor alpha (TGF-α) and epidermal growth factor receptor (EGFR). Expression of TGF-α protein, measured by immunohistochemistry, was higher in 94% of the squamous cell carcinomas and 87% of the foci of alveolar epithelial squamous metaplasia than that exhibited by the normal-appearing, adjacent lung parenchyma. In contrast, only 20% of adenocarcinomas and foci of epithelial hyperplasia expressed elevated levels of TGF-α. Many neoplasms expressing TGF-α also expressed excessive levels of EGFR mRNA. Southern and DNA slot blot analyses showed that the elevated EGFR expression was not due to amplification of the EGFR gene. These data suggest that increased amounts of TGF-α were early alterations in the progression of plutonium-induced squamous cell carcinoma, and these increases may occur in parallel with overexpression of the receptor for this growth factor. Together, these alterations create a potential autocrine loop for sustaining clonal expansion of cells initiated by high-LET radiation.
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Expression of TGF-α protein, measured by immunohistochemistry, was higher in 94% of the squamous cell carcinomas and 87% of the foci of alveolar epithelial squamous metaplasia than that exhibited by the normal-appearing, adjacent lung parenchyma. In contrast, only 20% of adenocarcinomas and foci of epithelial hyperplasia expressed elevated levels of TGF-α. Many neoplasms expressing TGF-α also expressed excessive levels of EGFR mRNA. Southern and DNA slot blot analyses showed that the elevated EGFR expression was not due to amplification of the EGFR gene. These data suggest that increased amounts of TGF-α were early alterations in the progression of plutonium-induced squamous cell carcinoma, and these increases may occur in parallel with overexpression of the receptor for this growth factor. 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identifier ISSN: 0033-7587
ispartof Radiation Research, 1994-11, Vol.140 (2), p.191-198
issn 0033-7587
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language eng
recordid cdi_crossref_primary_10_2307_3578903
source MEDLINE; JSTOR Archive Collection A-Z Listing
subjects Adenocarcinoma
Animals
Biological and medical sciences
BIOLOGICAL RADIATION EFFECTS
BIOLOGY AND MEDICINE, APPLIED STUDIES
BIOLOGY AND MEDICINE, BASIC STUDIES
Carcinoma, Squamous Cell - etiology
Carcinoma, Squamous Cell - metabolism
Cell lines
DNA
ENZYME IMMUNOASSAY
Female
GENE AMPLIFICATION
Growth factor receptors
GROWTH FACTORS
Immunohistochemistry
Lesions
LET
Lung neoplasms
Lung Neoplasms - etiology
Lung Neoplasms - metabolism
LUNGS
Medical sciences
Neoplasia
NEOPLASMS
Neoplasms, Radiation-Induced - metabolism
Plutonium - toxicity
PLUTONIUM 239
Pneumology
Rats
Rats, Inbred F344
Receptor, Epidermal Growth Factor - analysis
Receptor, Epidermal Growth Factor - biosynthesis
RNA
Squamous cell carcinoma
Transforming Growth Factor alpha - analysis
Transforming Growth Factor alpha - biosynthesis
Tumors of the respiratory system and mediastinum
title Expression of Transforming Growth Factor Alpha and Epidermal Growth Factor Receptor in Rat Lung Neoplasms Induced by Plutonium-239
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