Sonic hedgehog signalling proteins are frequently expressed in retinoblastoma and are associated with aggressive clinicopathological features
Sonic hedgehog signalling proteins are frequently expressed in retinoblastoma and are associated with aggressive clinicopathological features
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DOI：
10.1136/jclinpath-2014-202434
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发表时间：
2014-10
影响因子：
3.4
通讯作者：
J. Choe;J. Yun;Y. Jeon;S. H. Kim;H. Choung;Sohee Oh;Mira Park;J. Kim
中科院分区：
文献类型：
--
作者：
J. Choe;J. Yun;Y. Jeon;S. H. Kim;H. Choung;Sohee Oh;Mira Park;J. Kim
目的探讨SHH信号蛋白在视网膜母细胞瘤中的表达及其临床意义。方法采用免疫组化方法对79例去核视网膜母细胞瘤进行免疫组化研究，采用SHH、胶质瘤相关癌基因同源物（GLI） 1、GLI2、GLI3和ABC结合盒G2 （ABCG2）等SHH通路蛋白抗体。在两种视网膜母细胞瘤细胞系中进行了SHH信号蛋白的Western blotting。结果绝大多数视网膜母细胞瘤（78 / 79,98.7%）表达SHH，其中21例（26.6%）表达强烈。GLI1和GLI2也频繁表达：78例中有67例（85.9%），77例中有71例（92.2%）。GLI3是一种转录抑制因子，78例患者中有23例（29.5%）表达水平较低。78例患者中有23例ABCG2高表达（29.5%）。western blotting证实这些蛋白在视网膜母细胞瘤细胞系中高表达。SHH的表达与晚期、局部侵袭和转移相关（均p<0.05）。结论SHH信号分子在视网膜母细胞瘤肿瘤细胞中频繁表达，且高表达与疾病进展密切相关。我们的研究结果表明SHH信号通路可能在视网膜母细胞瘤的进展中发挥作用。
Aims This study aimed to examine the expression of Sonic hedgehog (SHH) signalling proteins in retinoblastoma and to evaluate its clinical significance. Methods Seventy-nine enucleated retinoblastoma tumours were investigated immunohistochemically using antibodies against SHH pathway proteins, such as SHH, glioma-associated oncogene homologue (GLI) 1, GLI2, GLI3 and ABC binding cassette G2 (ABCG2). Western blotting of SHH signalling proteins was performed in two retinoblastoma cell lines. Results SHH was expressed in most retinoblastoma cases (78 of 79, 98.7%), with 21 cases (26.6%) showing strong expression. GLI1 and GLI2 were also frequently expressed: 67 of 78 cases (85.9%) and 71 of 77 cases (92.2%), respectively. GLI3, a transcriptional repressor, was expressed at low levels in 23 of the 78 cases (29.5%). High ABCG2 expression was found in 23 of the 78 cases (29.5%). High expression levels of these proteins in retinoblastoma cell lines were confirmed by western blotting. The expression of SHH was associated with advanced stages, local invasion and metastasis (all p<0.05). Conclusions SHH signalling molecules were frequently expressed in retinoblastoma tumour cells, and high SHH expression was closely related to an advanced disease status. Our results suggest that the SHH signalling pathway may play a role in the progression of retinoblastoma.