Melphalan inhibits adenoma development through modulating the expression of K-ras-specific markers in K-ras Tg mice

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Title
Melphalan inhibits adenoma development through modulating the expression of K-ras-specific markers in K-ras Tg mice
Author(s)
S Lee; H Choi; E Kim; H Kim; Young-Ho Park; Dae Yeul Yu; S J Yoon; J Kim; Y Sheen; S N Park; D Y Yoon
Bibliographic Citation
International Journal of Oncology, vol. 37, no. 1, pp. 219-228
Publication Year
2010
Abstract
In previous research, we focused on the discovery of K-ras biomarkers, and effects of genotoxic carcinogens on their expression were investigated in this study. It is well-known that mutated K-ras gene is involved in ∼30% of human cancers such as lung cancer. To search for K-ras oncogene-induced modulators in lung tissues of K-ras transgenic mice, we analyzed K-ras-specific genes and proteins related to cancer development, signal transduction, inflammation as well as tumor suppression in a previous study. In this study, we investigated the modulating effects of genotoxic carcinogen treatment on expression of K-ras-dependent modulated genes and proteins in lung tissues of K-ras Tg mice. In order to evaluate candidate K-ras markers modulated by genotoxic stress and to investigate whether a genotoxic carcinogen would enhance or inhibit carcinogenesis in lung tissues of the K-ras Tg mice, the anti-cancer drug melphalan was intraperitoneally injected into K-ras Tg mice every two days for four weeks. RT-qPCR and proteomics analyses were performed in order to confirm whether K-ras-specific biomarkers would be modulated by melphalan treatment in K-ras Tg mice. The decreased adenomas were histopathologically observed and K-ras expression was suppressed in melphalan-treated K-ras Tg mice. Melphalan also recovered the expression of K-ras-dependent modulated biomarkers. These results suggest that melphalan inhibits carcinogenesis via modulating K-ras-specific genes and proteins expressed in the lung tissues of K-ras Tg mice.
Keyword
CancerK-ras oncogeneMelphalanProteomicsTg mouse
ISSN
1019-6439
Publisher
Spandidos Publ Ltd
DOI
http://dx.doi.org/10.3892/ijo-00000670
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Futuristic Animal Resource & Research Center > 1. Journal Articles
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