Tyrosine kinase inhibitor Imatinib mesylate alters DMBA-induced early onco/suppressor-gene expression with tissue-specificity in mice
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 proto-oncogenes and tumor suppressor genes after DMBA (7,12- dimethylbenz[a]anthracene) t...
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2019
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| Sorozat: | BIOMED RESEARCH INTERNATIONAL
2019 |
| doi: | 10.1155/2019/8670398 |
| mtmt: | 30400013 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/17029 |
| Tartalmi kivonat: | 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 proto-oncogenes 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 to examine the short-term possible anti-neoplastic and chemo-preventive 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, 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 down-regulations 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, 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 chemo-preventive potential of imatinib mesylate in cancer. |
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| Terjedelem/Fizikai jellemzők: | Terjedelem: 12 p-Azonosító: 8670398 |
| ISSN: | 2314-6133 |