Wang, Pan and Song, Xinhua and Cao, Dan and Cui, Kairong and Wang, Jingxiao and Utpatel, Kirsten and Shang, Runze and Wang, Haichuan and Che, Li and Evert, Matthias and Zhao, Keji and Calvisi, Diego F. and Chen, Xin (2020) Oncogene-dependent function of BRG1 in hepatocarcinogenesis. CELL DEATH & DISEASE, 11 (2): 91. ISSN 2041-4889,
Full text not available from this repository. (Request a copy)Abstract
Hepatocellular carcinoma (HCC) is the major type of primary liver cancer. Genomic studies have revealed that HCC is a heterogeneous disease with multiple subtypes. BRG1, encoded by the SMARCA4 gene, is a key component of SWI/SNF chromatin-remodeling complexes. Based on TCGA studies, somatic mutations of SMARCA4 occur in similar to 3% of human HCC samples. Additional studies suggest that BRG1 is overexpressed in human HCC specimens and may promote HCC growth and invasion. However, the precise functional roles of BRG1 in HCC remain poorly delineated. Here, we analyzed BRG1 in human HCC samples as well as in mouse models. We found that BRG1 is overexpressed in most of human HCC samples, especially in those associated with poorer prognosis. BRG1 expression levels positively correlate with cell cycle and negatively with metabolic pathways in the Cancer Genome Atlas (TCGA) human HCC data set. In a murine HCC model induced by c-MYC overexpression, ablation of the Brg1 gene completely repressed HCC formation. In striking contrast, however, we discovered that concomitant deletion of Brg1 and overexpression of c-Met or mutant NRas (NRAS(V12)) triggered HCC formation in mice. Altogether, the present data indicate that BRG1 possesses both oncogenic and tumor-suppressing roles depending on the oncogenic stimuli during hepatocarcinogenesis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RAPAMYCIN COMPLEX 1; C-MYC; MAMMALIAN TARGET; TUMOR-SUPPRESSOR; CHROMATIN; SWI/SNF; EXPRESSION; TRANSFECTION; ACTIVATION; PATHWAYS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2021 11:17 |
| Last Modified: | 09 Apr 2021 11:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45148 |
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