SETDB1 accelerates tumourigenesis by regulating the WNT signalling pathway
Citations Over TimeTop 13% of 2014 papers
Abstract
We investigated the oncogenic role of SETDB1, focusing on non-small cell lung cancer (NSCLC), which has high expression of this protein. A total of 387 lung cancer cases were examined by immunohistochemistry; 72% of NSCLC samples were positive for SETDB1 staining, compared to 46% samples of normal bronchial epithelium (106 cases) (p <0.0001). The percentage of positive cells and the intensity of staining increased significantly with increased grade of disease. Forced expression of SETDB1 in NSCLC cell lines enhanced their clonogenic growth in vitro and markedly increased tumour size in a murine xenograft model, while silencing (shRNA) SETDB1 in NSCLC cells slowed their proliferation. SETDB1 positively stimulated activity of the WNT-β-catenin pathway and diminished P53 expression, resulting in enhanced NSCLC growth in vitro and in vivo. Our finding suggests that therapeutic targeting of SETDB1 may benefit patients whose tumours express high levels of SETDB1.
Related Papers
- Clonogenic and nonclonogenic in vitro chemosensitivity assays.(1985)
- → Correlation of drug response in patients and in the clonogenic assay with solid human tumour xenografts(1990)61 cited
- → The deensity of clonogenic cless in human solid tumors(1991)16 cited
- → Abstract 5497: An efficient clonogenic assay for cytotoxic drug screening(2010)2 cited
- Comparison of measurement of surviving tumor cells by growth and clonogenic assays(1999)