Department of Biopharmaceutical Sciences, College of Pharmacy and Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA.
Oncogene. 2011 Jan 20;30(3):356-65. doi: 10.1038/onc.2010.426. Epub 2010 Sep 20.
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.
我们之前的研究表明，两个剪接因子，多嘧啶 tract-binding 蛋白（PTB）和 SRp20，在上皮性卵巢癌（EOC）中上调，敲低 PTB 表达抑制卵巢肿瘤细胞生长和转化特性。在本报告中，我们表明，在卵巢癌细胞中敲低 SRp20 的表达也会导致肿瘤细胞在软琼脂中的生长和集落形成受到实质性抑制，这种抑制的程度似乎与 SRp20 的抑制程度相关。SRp20 的大量敲低会引发这些细胞的显著凋亡。这些结果表明，SRp20 的过表达是卵巢肿瘤细胞生长和存活所必需的。对两个专门的组织微阵列进行的 PTB 和 SRp20 的免疫组织化学染色，一个包含良性卵巢肿瘤、交界性/低恶性潜能（LMP）卵巢肿瘤以及侵袭性 EOC，另一个包含从 I 期到 IV 期疾病的侵袭性 EOC，揭示了 PTB 和 SRp20 在良性肿瘤和侵袭性 EOC 之间以及交界性/LMP 肿瘤和侵袭性 EOC 之间的表达存在差异。在良性肿瘤中，全阴性或混合染色的病例（每个病例至少有两个可评估的切片核心）比侵袭性 EOC 多，而侵袭性 EOC 中全阳性染色的病例比其他两种疾病分类多。在侵袭性 EOC 中，大多数病例的 PTB 和 SRp20 均为全阳性染色，并且任何肿瘤分期之间的平均染色或阳性癌细胞频率均无显著差异。因此，PTB 和 SRp20 的表达与卵巢肿瘤的恶性程度相关，但与侵袭性 EOC 的分期无关。
