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

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Péter Attila Gergely, Balázs Murnyák, János Bencze, Andrea Kurucz, Timea Varjas, Katalin Gombos, Tibor Hortobágyi

Original languageEnglish
Article number8670398
JournalBioMed Research International
Volume2019
DOIs
Published1 Jan 2019

King's Authors

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 of Hras, Kras, Myc, and Trp53 genes in the brain, bone marrow, spleen, liver, abdominal lymph nodes, thymus, lungs, and kidneys, respectively. 24 hours after the imatinib mesylate injection, we observed significant Kras downregulation in the bone marrow and lung of the DMBA-treated mice. Moreover, the mRNA expression of Myc was also found to be decreased significantly in the spleen. Interestingly, while Trp53 expression was significantly increased in the lung, it was decreased in the other tissues. However, there was also a tendency in the decreased Myc level in the bone marrow, brain, kidneys, lungs, and lymph nodes and in the decreased Hras level 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 expression in vivo, supporting the chemopreventive potential of imatinib mesylate in cancer.

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