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

Abstract

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 wellknown 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-rasdependent 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-rasdependent modulated biomarkers. These results suggest that melphalan inhibits carcinogenesis via modulating K-rasspecific genes and proteins expressed in the lung tissues of K-ras Tg mice.

Leukotriene B4 receptor-2 contributes to KRAS-driven lung tumor formation by promoting interleukin-6-mediated inflammation

“…Kras G12D mice were kindly provided by Professor Dae-Yeol Yu, who generated these mice via DNA microinjection into B6D2F1 strain (BDF-1) mouse embryos as previously described 22 ; a KrasG12D gene expression vector containing the hSP-C promoter was used to drive lung-specific expression of the KrasG12D gene. BLT2 KO mice were constructed as previously described 23 .…”