Journal article
Radiation-enhanced lung cancer progression in a transgenic mouse model of lung cancer is predictive of outcomes in human lung and breast cancer
Clinical cancer research, Vol.20(6), pp.1610-1622
03/15/2014
DOI: 10.1158/1078-0432.CCR-13-2589
PMCID: PMC3961755
PMID: 24486591
Abstract
Carcinogenesis is an adaptive process between nascent tumor cells and their microenvironment, including the modification of inflammatory responses from antitumorigenic to protumorigenic. Radiation exposure can stimulate inflammatory responses that inhibit or promote carcinogenesis. The purpose of this study is to determine the impact of radiation exposure on lung cancer progression in vivo and assess the relevance of this knowledge to human carcinogenesis. K-ras(LA1) mice were irradiated with various doses and dose regimens and then monitored until death. Microarray analyses were performed using Illumina BeadChips on whole lung tissue 70 days after irradiation with a fractionated or acute dose of radiation and compared with age-matched unirradiated controls. Unique group classifiers were derived by comparative genomic analysis of three experimental cohorts. Survival analyses were performed using principal component analysis and k-means clustering on three lung adenocarcinoma, three breast adenocarcinoma, and two lung squamous carcinoma annotated microarray datasets. Radiation exposure accelerates lung cancer progression in the K-ras(LA1) lung cancer mouse model with dose fractionation being more permissive for cancer progression. A nonrandom inflammatory signature associated with this progression was elicited from whole lung tissue containing only benign lesions and predicts human lung and breast cancer patient survival across multiple datasets. Immunohistochemical analyses suggest that tumor cells drive predictive signature. These results demonstrate that radiation exposure can cooperate with benign lesions in a transgenic model of cancer by affecting inflammatory pathways, and that clinically relevant similarities exist between human lung and breast carcinogenesis.
Details
- Title: Subtitle
- Radiation-enhanced lung cancer progression in a transgenic mouse model of lung cancer is predictive of outcomes in human lung and breast cancer
- Creators
- Oliver Delgado - The University of Texas Southwestern Medical CenterKimberly G Batten - The University of Texas Southwestern Medical CenterJames A Richardson - The University of Texas Southwestern Medical CenterXian-Jin Xie - The University of Texas Southwestern Medical CenterAdi F Gazdar - The University of Texas Southwestern Medical CenterAadil A Kaisani - The University of Texas Southwestern Medical CenterLuc Girard - The University of Texas Southwestern Medical CenterCarmen Behrens - The University of Texas MD Anderson Cancer CenterMilind Suraokar - The University of Texas MD Anderson Cancer CenterGail Fasciani - The University of Texas Southwestern Medical CenterWoodring E Wright - The University of Texas Southwestern Medical CenterMichael D Story - The University of Texas Southwestern Medical CenterIgnacio I Wistuba - The University of Texas MD Anderson Cancer CenterJohn D Minna - The University of Texas Southwestern Medical CenterJerry W Shay - King Abdulaziz University
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.20(6), pp.1610-1622
- Publisher
- United States
- DOI
- 10.1158/1078-0432.CCR-13-2589
- PMID
- 24486591
- PMCID
- PMC3961755
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Grant note
- 1P30CA142543 / NCI NIH HHS CA-16672 / NCI NIH HHS P30 CA016672 / NCI NIH HHS P30 CA142543 / NCI NIH HHS P50 CA070907 / NCI NIH HHS P50CA70907 / NCI NIH HHS
- Language
- English
- Date published
- 03/15/2014
- Academic Unit
- Preventive and Community Dentistry; Biostatistics; Dental Research
- Record Identifier
- 9983917671002771
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