Knockdown of splicing factor SRp20 causes apoptosis in ovarian cancer cells and its expression is associated with malignancy of epithelial ovarian cancer.
Knockdown of splicing factor SRp20 causes apoptosis in ovarian cancer cells and its expression is associated with malignancy of epithelial ovarian cancer.
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DOI：
10.1038/onc.2010.426
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发表时间：
2011-01-20
期刊：
影响因子：
8
通讯作者：
Beck, W. T.
中科院分区：
文献类型：
--
作者：
He, X.;Arslan, A. D.;Pool, M. D.;Ho, T-T;Darcy, K. M.;Coon, J. S.;Beck, W. T.
关键词：
我们以前的研究表明，两个剪接因子，多聚嘧啶片段结合蛋白（PTB）和SRp 20，在上皮性卵巢癌（EOC）中上调，PTB表达的敲低抑制卵巢肿瘤细胞的生长和转化特性。在这份报告中，我们表明，在卵巢癌细胞中SRp 20表达的敲低也会导致实质性抑制肿瘤细胞生长和软琼脂中的集落形成，这种抑制的程度似乎与SRp 20的抑制程度相关。SRp 20表达的大量敲低引发这些细胞中的显著凋亡。这些结果表明SRp 20的过度表达是卵巢肿瘤细胞生长和存活所必需的。两个专门的组织微阵列（TMA），一个包含良性卵巢肿瘤，交界性/低恶性潜能（LMP）卵巢肿瘤以及浸润性EOC和其他包含浸润性EOC的免疫组织化学染色从I期到IV期疾病，揭示了PTB和SRp 20都表达差异良性肿瘤和浸润性EOC之间，和交界性/LMP肿瘤和浸润性EOC之间。良性肿瘤中全阴性或混合染色病例（每例至少有两个可评价切片芯）多于浸润性EOC，而浸润性EOC中全阳性染色病例多于其他两种疾病分类。在侵袭性EOC中，绝大多数病例PTB和SRp 20染色均为阳性，并且在任何肿瘤阶段之间阳性癌细胞的平均染色或频率没有显著差异。因此，PTB和SRp 20的表达与卵巢肿瘤的恶性程度有关，而与卵巢癌的浸润性分期无关。
Our previous study revealed that two splicing factors, polypyrimidine tract-binding protein (PTB) and SRp20, were up-regulated 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 (TMAs), 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 while there were more all positive staining cases in invasive EOC than in the other two disease classifications. Among invasive EOC, the great 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.
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