Autor: |
Ji Hae Lee, Jee Young Sung, Eun Kyung Choi, Hyun-Kyoung Yoon, Bo Ram Kang, Eun Kyung Hong, Byung-Kiu Park, Yong-Nyun Kim, Seung Bae Rho, Kyungsil Yoon |
Jazyk: |
angličtina |
Rok vydání: |
2019 |
Předmět: |
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Zdroj: |
Cells, Vol 8, Iss 2, p 145 (2019) |
Druh dokumentu: |
article |
ISSN: |
2073-4409 |
DOI: |
10.3390/cells8020145 |
Popis: |
The CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that regulates cellular proliferation, differentiation, apoptosis and tumorigenesis. Although the pro-oncogenic roles of C/EBPβ have been implicated in various human cancers, how it contributes to tumorigenesis or tumor progression has not been determined. Immunohistochemistry with human non-small cell lung cancer (NSCLC) tissues revealed that higher levels of C/EBPβ protein were expressed compared to normal lung tissues. Knockdown of C/EBPβ by siRNA reduced the proliferative capacity of NSCLC cells by delaying the G2/M transition in the cell cycle. In C/EBPβ-knockdown cells, a prolonged increase in phosphorylation of cyclin dependent kinase 1 at tyrosine 15 (Y15-pCDK1) was displayed with simultaneously increased Wee1 and decreased Cdc25B expression. Chromatin immunoprecipitation (ChIP) analysis showed that C/EBPβ bound to distal promoter regions of WEE1 and repressed WEE1 transcription through its interaction with histone deacetylase 2. Treatment of C/EBPβ-knockdown cells with a Wee1 inhibitor induced a decrease in Y15-pCDK1 and recovered cells from G2/M arrest. In the xenograft tumors, the depletion of C/EBPβ significantly reduced tumor growth. Taken together, these results indicate that Wee1 is a novel transcription target of C/EBPβ that is required for the G2/M phase of cell cycle progression, ultimately regulating proliferation of NSCLC cells. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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