Melphalan inhibits adenoma development through modulating the expression of K-ras-specific markers in K-ras Tg mice.
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 approximately 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.
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong 1, Gwangjin-gu, Seoul 143-701, Korea.
Sojung
S
Lee
Heesook
H
Choi
Eunjin
E
Kim
Heejong
H
Kim
Young-Ho
YH
Park
Dae-Yeul
DY
Yu
Seok-Joo
SJ
Yoon
Jinman
J
Kim
Yhunyhong
Y
Sheen
Sue-Nie
SN
Park
Do-Young
DY
Yoon
D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008558:Melphalan / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological
D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D008558:Melphalan