Krüppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis
| Autor: | Kyoung-Sun Lee, Seung-Ho Heo, Yang-Kyu Choi, Woon Kyu Lee, Eui-Suk Jeong, Jin‑Hee Seo |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Cancer Research Kruppel-Like Transcription Factors Receptor Transforming Growth Factor-beta Type I SMAD Protein Serine-Threonine Kinases Biology medicine.disease_cause Transforming Growth Factor beta1 Mice Cyclin D1 medicine Animals RNA Messenger Smad3 Protein Cell Proliferation Mice Knockout Oncogene Incidence Tumor Suppressor Proteins Liver Neoplasms Cancer General Medicine Cell cycle medicine.disease Mice Inbred C57BL Cell Transformation Neoplastic Oncology Early Growth Response Transcription Factors Cancer research Liver cancer Carcinogenesis Receptors Transforming Growth Factor beta Signal Transduction Transforming growth factor |
| Zdroj: | Oncology Reports. 33:2037-2044 |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2015.3801 |
| Popis: | Liver cancer is the third most common cancer, and the incidence as well as the mortality rate of liver cancer are on the increase. There are many signaling pathways that are involved in hepatic tumorigenesis. One of these pathways, the transforming growth factor-β (TGF-β)/Smad pathway with KLF10, has been reported to suppress cellular proliferation in most cases. However, the actual functions of KLF10 in various pathophysiological conditions are still fragmentary and unclear. In the present study, the practical role of KLF10 in DEN-induced hepatic carcinogenesis, was elucidated using KLF10 null mice. In the necropsy and histopathological analysis, KLF10 KO mice exhibited lower tumor incidence and PCNA labeling indices than these values in the wild-type mice. Additional analyses revealed that the mRNA and protein levels of Smad3, TGF-β1, TGF-β RI and p15 were increased in the tumor tissues of the KLF10 KO mice, while those of cMyc and cyclin D1 were downregulated. The level of phospho-Smad3 was also significantly higher in the tumor tissues of the KLF10 KO mice. All together, the KLF10 KO condition may reinforce the TGF-β‑Smad signaling pathway and confer tumor-suppressor effects against chemically induced liver tumorigenesis. |
| Databáze: | OpenAIRE |
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