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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Tnfa and Il-10 Deficiencies Have Contrasting Effects on Lung Tumor Susceptibility: Gender-Dependent Modulation of IL-10 Haploinsufficiency
Molecular Carcinogenesis, Volume 38, No. 3, Year 2003
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Description
Epidemiologic evidence suggests that pulmonary diseases with a prominent chronic inflammatory component elevate lung cancer risk. Genetic manipulations of mouse models of lung inflammation and tumorigenesis can be used to investigate this association. The genes encoding pro-inflammatory tumor necrosis factor-α (TNFα) and anti-inflammatory IL-10 cytokines map within quantitative trait loci that regulate susceptibility to lung tumor development in mice; sensitive A/J and resistant C57BL/6J (B6) mice have different Tnfa and II-10 alleles. Genetic ablation studies were performed to examine whether these genes would qualify as candidate tumor modifiers. Tnfa null (-/-) mice on a B6 background and B6.129 II-10-/- mice were intercrossed with A/J mice and subjected to urethane carcinogenesis; lung tumor multiplicity was determined 20 weeks later. In the absence of one copy of Tnfa, tumor number. Male II-10+/+ mice developed more tumors than did female mice (P<0.001), absence of one copy of II-10 raised tumor number in female mice to that observed in +/+ males, but no change in multiplicity occurred in II-70 hemizygous males. Thus, a deficit of pro-inflammatory TNFα decreased the number of tumors, whereas diminished gene copy number of anti-inflammatory IL-10 increased tumorigenesis; manifestation of an effect of II-10 haploinsufficiency is gender dependent. These studies support a role for inflammation in lung cancer susceptibility. © 2003 Wiley-Liss, Inc.
Authors & Co-Authors
Bernert, Heike
United States, Columbus
The Ohio State University Comprehensive Cancer Center
Sekikawa, Kenji
Japan, Tsukuba
Institute of Agrobiological Sciences, Naro
Radcliffe, Richard A.
United States, Aurora
University of Colorado Anschutz Medical Campus
Iraqi, Fuad A.
Kenya, Nairobi
International Livestock Research Institute Nairobi
You, Ming
United States, St. Louis
Washington University School of Medicine in St. Louis
Malkinson, Alvin M.
United States, Aurora
University of Colorado Anschutz Medical Campus
United States, Aurora
University Colorado Cancer Center
Statistics
Citations: 37
Authors: 6
Affiliations: 6
Identifiers
Doi:
10.1002/mc.10151
ISSN:
08991987
Research Areas
Cancer
Genetics And Genomics
Study Approach
Quantitative
Participants Gender
Male
Female