Krüppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis

Heo,Seung-Ho; Jeong,Eui-Suk; Lee,Kyoung-Sun; Seo,Jin‑Hee; Lee,Woon-Kyu; Choi,Yang-Kyu

doi:10.3892/or.2015.3801

Krüppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis

Authors:
- Seung-Ho Heo
- Eui-Suk Jeong
- Kyoung-Sun Lee
- Jin‑Hee Seo
- Woon-Kyu Lee
- Yang-Kyu Choi
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Affiliations: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea, Laboratory Animal Center, Osong Medical Innovation Foundation, Chungbuk 363-951, Republic of Korea, Laboratory Animal Facility, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea, Laboratory of Developmental Genetics, College of Medicine, Inha University, Incheon 402-751, Republic of Korea
Published online on: February 13, 2015 https://doi.org/10.3892/or.2015.3801
Pages: 2037-2044

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Abstract

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.

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