Tyrosine Kinase Inhibitor Imatinib Mesylate Alters DMBA-Induced Early Onco/Suppressor Gene Expression with Tissue-Specificity in Mice

Abstract

Tyrosine kinases play crucial roles in cellular development and tumorigenesis. Tyrosine kinase inhibitors (TKIs) are effective and widely used drug molecules in targeted cancer therapies. Altered expressions of protooncogenes and tumor suppressor genes after DMBA (7,12-dimethylbenz[a]anthracene) treatment have been described as early markers of tumor induction; however their tissue-specific effects remain still unclear. Our study was aimed at examining the short-term possible antineoplastic and chemopreventive effects of a TKI compound (imatinib mesylate) on a DMBA-induced mouse tumor model. In addition, we also investigated the tissue-specific expressions ofHras, Kras, Myc,andTrp53genes in the brain, bone marrow, spleen, liver, abdominal lymph nodes, thymus, lungs, and kidneys, respectively. 24 hours after the imatinib mesylate injection, we observed significantKrasdownregulation in the bone marrow and lung of the DMBA-treated mice. Moreover, the mRNA expression ofMycwas also found to be decreased significantly in the spleen. Interestingly, whileTrp53expression was significantly increased in the lung, it was decreased in the other tissues. However, there was also a tendency in the decreasedMyclevel in the bone marrow, brain, kidneys, lungs, and lymph nodes and in the decreasedHraslevel in the bone marrow, kidneys, and lungs, although no significant differences were observed. Our findings indicate rapid tissue-specific impact of imatinib mesylate on DMBA-induced gene expressionin vivo,supporting the chemopreventive potential of imatinib mesylate in cancer.