Dataset Information

Decreased Interferon Alpha/Beta Signature Associated with Human Lung Tumorigenesis.

ABSTRACT: Accumulating evidence suggests that interferon (IFN) alpha/beta are involved in antitumor immunity and cancer immunoediting, but information on the antitumor effects of IFN alpha/beta in lung cancer is limited. In our study, we elucidated the IFN alpha/beta signature during both human fetal lung development and lung tumorigenesis. Our findings indicated gradual upregulation in the IFN alpha/beta signature during human fetal lung development. In addition, this signature was progressively downregulated in normal human airway epithelial cells from lung cancer patients, in immortalized human bronchial epithelial cell lines from later passages, in late-stage lung squamous cell carcinoma (LSCC) tissues, and in LSCC tissues exhibiting lymph node metastasis. Therefore, from its earliest stages, lung tumorigenesis may be associated with a decreased IFN alpha/beta signature. This association may provide insight to guide the detection of high-risk lung cancer patients.

SUBMITTER: Tong R

PROVIDER: S-EPMC4683557 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Decreased Interferon Alpha/Beta Signature Associated with Human Lung Tumorigenesis.

Tong Run R Feng Lin L Zhang Lei L Zhang Jianzhi J Mao Yousheng Y Zhang Kaitai K Gao Yanning Y Wang Guiqi G Cheng Shujun S

Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 20150826 12

Accumulating evidence suggests that interferon (IFN) alpha/beta are involved in antitumor immunity and cancer immunoediting, but information on the antitumor effects of IFN alpha/beta in lung cancer is limited. In our study, we elucidated the IFN alpha/beta signature during both human fetal lung development and lung tumorigenesis. Our findings indicated gradual upregulation in the IFN alpha/beta signature during human fetal lung development. In addition, this signature was progressively downregu ...[more]

PMID: 26308599

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Project description:Although mutations in Kras are present in 21% of lung tumors, there is a high level of heterogeneity in phenotype and outcomes amongst lung cancer patients suggesting the importance of other pathways. Wnt/β-catenin signaling is a known oncogenic pathway that plays a well defined role in colon and skin cancer but its role in lung cancer remains unclear. We show that activation of Wnt/β-catenin in the bronchiolar epithelium of the adult lung does not promote tumor development by itself. However, activation of Wnt/β- catenin signaling leads to a dramatic increase in tumor formation both in overall tumor number and size compared to KrasG12D alone. We show that activation of Wnt/β- catenin signaling significantly alters the KrasG12D tumor phenotype resulting in a phenotypic switch from bronchiolar epithelium to the highly proliferative distal progenitors found in the embryonic lung. This is associated with a decrease in E- cadherin expression at the cell surface which may increase metastasis in Wnt/β-catenin signaling positive tumors. Together, these data suggest that activation of Wnt/β-catenin signaling in combination with other oncogenic pathways in lung epithelium may lead to a more aggressive phenotype due to the imposition of an embryonic distal progenitor phenotype accompanied by decreased E-cadherin expression. We performed microarray analysis of control murine lung, CC10-cre:KrasG12D, and CC10-cre:Ctnnb1ex3flox:LSL-KrasG12D double mutant micro-dissected murine lung tumors to determine their transcriptional phenotype. Lungs of five-month-old mice were PBS inflated and all the tumors in each lobe were dissected. The total number of tumors obtained from three out of the 5 pulmonar lobes of each animal was called a sample the other two lobes were saved in case there were problems and the array needed to be repeated. Trizol was used to isolate RNA for microarray analysis. Samples & Genotypes: control murine lung n=2 animals, CC10-cre:KrasG12D n=2 animals, and CC10-cre:Ctnnb1ex3flox:LSL-KrasG12D n=2 animals.

Dataset Information

Decreased Interferon Alpha/Beta Signature Associated with Human Lung Tumorigenesis.

Publications

Decreased Interferon Alpha/Beta Signature Associated with Human Lung Tumorigenesis.

Similar Datasets

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