Knockdown of splicing factor SRp20 causes apoptosis in ovarian cancer cells and its expression is associated with malignancy of epithelial ovarian cancer
Open Access
- 20 September 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 30 (3), 356-365
- https://doi.org/10.1038/onc.2010.426
Abstract
Our previous study revealed that two splicing factors, polypyrimidine tract-binding protein (PTB) and SRp20, were upregulated in epithelial ovarian cancer (EOC) and knockdown of PTB expression inhibited ovarian tumor cell growth and transformation properties. In this report, we show that knockdown of SRp20 expression in ovarian cancer cells also causes substantial inhibition of tumor cell growth and colony formation in soft agar and the extent of such inhibition appeared to correlate with the extent of suppression of SRp20. Massive knockdown of SRp20 expression triggered remarkable apoptosis in these cells. These results suggest that overexpression of SRp20 is required for ovarian tumor cell growth and survival. Immunohistochemical staining for PTB and SRp20 of two specialized tissue microarrays, one containing benign ovarian tumors, borderline/low malignant potential (LMP) ovarian tumors as well as invasive EOC and the other containing invasive EOC ranging from stage I to stage IV disease, reveals that PTB and SRp20 are both expressed differentially between benign tumors and invasive EOC, and between borderline/LMP tumors and invasive EOC. There were more all-negative or mixed staining cases (at least two evaluable section cores per case) in benign tumors than in invasive EOC, whereas there were more all-positive staining cases in invasive EOC than in the other two disease classifications. Among invasive EOC, the majority of cases were stained all positive for both PTB and SRp20, and there were no significant differences in average staining or frequency of positive cancer cells between any of the tumor stages. Therefore, the expression of PTB and SRp20 is associated with malignancy of ovarian tumors but not with stage of invasive EOC.Keywords
This publication has 55 references indexed in Scilit:
- SRp20 and CUG-BP1 Modulate Insulin Receptor Exon 11 Alternative SplicingMolecular and Cellular Biology, 2009
- Chromatin Binding of SRp20 and ASF/SF2 and Dissociation from Mitotic Chromosomes Is Modulated by Histone H3 Serine 10 PhosphorylationMolecular Cell, 2009
- The BCL-2 protein family: opposing activities that mediate cell deathNature Reviews Molecular Cell Biology, 2008
- Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitroOncogene, 2007
- Understanding alternative splicing: towards a cellular codeNature Reviews Molecular Cell Biology, 2005
- Defects in Pre-mRNA Processing as Causes of and Predisposition to DiseasesDNA and Cell Biology, 2002
- Role of Polypyrimidine Tract Binding Protein in the Function of the Hepatitis B Virus Posttranscriptional Regulatory ElementJournal of Virology, 2001
- Heterogeneous Ribonucleoprotein A1 Is Part of an Exon-specific Splice-silencing Complex Controlled by Oncogenic Signaling PathwaysPublished by Elsevier BV ,2000
- Stage-specific changes in SR splicing factors and alternative splicing in mammary tumorigenesisOncogene, 1999
- On the Interpretation of χ 2 from Contingency Tables, and the Calculation of PJournal of the Royal Statistical Society, 1922