期刊
LABORATORY INVESTIGATION
卷 98, 期 7, 页码 957-967出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41374-018-0046-3
关键词
-
资金
- Assar Gabrielssons Research Foundation
- BioCARE National Strategic Research Program at University of Gothenburg
- BIOCEV [CZ.1.05/1.1.00/02.0109]
- Johan Jansson Foundation for Cancer Research
- Knut and Alice Wallenberg Foundation
- Sahlgrenska Academy (ALF) at University of Gothenburg [716321, 722211]
- Swedish Cancer Society [2016-438, 2015-7130]
- Swedish Research Council [2017-01392]
- Swedish Society for Medical Research
- Swedish Childhood Cancer Foundation [2017-0043]
- Wilhelm and Martina Lundgren Foundation for Scientific Research
- VINNOVA
- Wallenberg Center for molecular and translational medicine, University of Gothenburg, Sweden
FUS-DDIT3 belongs to the FET (FUS, EWSR1, and TAF15) family of fusion oncogenes, which collectively are considered to be key players in tumor development. Even though over 90% of all myxoid liposarcomas (MLS) have a FUS-DDIT3 gene fusion, there is limited understanding of the signaling pathways that regulate its expression. In order to study cell proliferation and FUS-DDIT3 regulation at mRNA and protein levels, we first developed a direct cell lysis approach that allows DNA, mRNA, and protein to be analyzed in the same sample using quantitative PCR, reverse transcription quantitative qPCR and proximity ligation assay, respectively. We screened 70 well-characterized kinase inhibitors and determined their effects on cell proliferation and expression of FUS-DDIT3 and FUS at both mRNA and protein levels in the MLS 402-91 cell line, where twelve selected inhibitors were evaluated further in two additional MLS cell lines. Both FUS-DDIT3 and FUS mRNA expression correlated with cell proliferation and both transcripts were co-regulated in most conditions, indicating that the common 5' FUS promotor is important in transcriptional regulation. In contrast, FUS-DDIT3 and FUS protein levels displayed more cell line dependent expression. Furthermore, most JAK inhibitors caused FUSDDIT3 downregulation at both mRNA and protein levels. In conclusion, defining factors that regulate FUS-DDIT3 expression opens new means to understand MLS development at the molecular level.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据