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Updated: Jun 27, 2026

Detection of Lung Tumor Progression in Mice by Ultrasound Imaging
Published on: February 27, 2020
Profiling of transcripts and proteins modulated by K-ras oncogene in the lung tissues of K-ras transgenic mice by
Sojung Lee1, Jungwoo Kang, Minchul Cho
1Department of Bioscience and Biotechnology, Konkuk University, Gwangjin-gu, Seoul 143-701, Korea.
Abstract:
The mutated K-ras gene is involved in approximately 30% of human cancers. In order to search for K-ras oncogene-induced modulators in lung tissues of K-ras transgenic mice, we performed microarray and proteomics (LC/ESI-MS/MS) analysis. Genes (RAB27b RAS family, IL-1RA, IL-33, chemokine ligand 6, epiregulin, EGF-like domain and cathepsin) related to cancer development (Wnt signaling pathway) and inflammation (chemokine/cytokine signaling pathway, Toll receptor signaling) were up-regulated while genes (troponin, tropomodulin 2, endothelial lipase, FGFR4, integrin alpha8 and adenylate cyclase 8) related to the tumor suppression such as p53 pathway, TGF-beta signaling pathway and cadherin signaling pathway were down-regulated by K-ras oncogene. Proteomics approach revealed that up-regulated proteins in lung adenomas of K-ras mice were classified as follows: proteins related to the metabolism/catabolism (increased from 7 to 22% by K-ras gene), proteins related to translation/transcription and nucleotide (from 4 to 6%), proteins related to signal transduction (from 3 to 5%), proteins related to phosphorylation (from 1 to 2%). ATP synthase, Ras oncogene family, cytochrome c oxidase, flavoprotein, TEF 1, adipoprotein A-1 BP, glutathione oxidase, fatty acid BP 4, diaphorase 1, MAPK4 and transgelin were up-regulated by K-ras oncogene. However, integrin alpha1, Ras-interacting protein (Rain), endothelin-converting enzyme-1d and splicing factor 3b were down-regulated. These studies suggest that genes related to cancer development and inflammation were up-regulated while genes related to the tumor suppression were down-regulated by K-ras, resulting in the tumor growth. Putative biomarkers such as cell cycle related genes (Cdc37), cancer cell adhesion (Glycam 1, integrin alpha8, integrin alphaX and Clec4n), signal transduction (Tlr2, IL-33, and Ccbp2), migration (Ccr1, Ccl6, and diaphorase 1 (Cyb5r3) and cancer development (epiregulin) can be useful for diagnosis and as prognosis markers and some of the target molecules can be applied for prevention of cancer.
Insights
The K-ras oncogene promotes cancer by up-regulating genes linked to tumor growth and inflammation while down-regulating tumor suppressor genes. This research identifies potential biomarkers for cancer diagnosis and prevention.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The mutated K-ras gene is implicated in approximately 30% of human cancers.
- Understanding K-ras oncogene-induced molecular changes is crucial for cancer research.
Purpose of the Study:
- To identify K-ras oncogene-induced modulators in lung tissues of K-ras transgenic mice.
- To explore potential biomarkers for cancer diagnosis and prevention.
Main Methods:
- Microarray analysis to assess gene expression.
- Proteomics (LC/ESI-MS/MS) to identify protein level changes.
- Utilized K-ras transgenic mouse models for lung tissue analysis.
Main Results:
- K-ras oncogene up-regulated cancer/inflammation-related genes (e.g., Wnt, chemokine/cytokine signaling) and down-regulated tumor suppressor genes (e.g., p53, TGF-beta pathways).
- Proteomics revealed increased metabolism/catabolism, translation/transcription, signal transduction, and phosphorylation proteins.
- Identified specific up-regulated proteins (e.g., ATP synthase, Ras family) and down-regulated proteins (e.g., integrin alpha1, Rain).
Conclusions:
- K-ras oncogene drives tumor growth by altering gene and protein expression, favoring cancer development and suppressing tumor suppression mechanisms.
- Identified potential biomarkers (e.g., Cdc37, Glycam 1, IL-33, Ccl6, epiregulin) for cancer diagnosis, prognosis, and therapeutic targets.
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