The transcriptome of nonpolypoid and polypoid preinvasive lesions of the human large intestine
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE21962 | GEO | 2010/05/27
SECONDARY ACCESSION(S): PRJNA126771
REPOSITORIES: GEO
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Project description:Basic studies on preneoplastic lesions are important to determine the molecular alterations that take place in early steps of lung carcinogenesis. Little is known about the molecular events preceding the development of lung cancer in the context of an inflammatory environment. In this study we report the generation of a chemical-induced lung carcinogenesis mouse model in the presence of silicotic chronic inflammation. Silica-induced lung inflammation, strongly promoted incidence of lung cancer in mice treated with NDMA, a carcinogen found in tobacco smoke. Histological and molecular analysis revealed that permanent inflammation contributed to lung tumorigenesis through the adquisition of preneoplastic changes in lung epithelial cells. Inflammatory milieu increased the expression of PDCD1, TGFβ-1, MCP-1, LAG3, and Foxp3 and the presence of regulatory T cells within preneoplastic lesions. In addition concomitant chronic inflammation changed the K-ras mutational profile of the generated tumors from Q61R to G12D transition. In summary, these data identify early molecular mechanisms underlying lung carcinogenesis in an inflammatory context at different steps, providing a novel approach for the identification of drivers from preneoplastic to neoplastic lesions
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