A homeobox protein, Prox1, is involved in the differentiation, proliferation, and prognosis in hepatocellular carcinoma
A homeobox protein, Prox1, is involved in the differentiation, proliferation, and prognosis in hepatocellular carcinoma
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DOI：
10.1158/1078-0432.ccr-06-0712
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发表时间：
2006-10-15
影响因子：
11.5
通讯作者：
Kubo, Hajime
中科院分区：
文献类型：
--
作者：
Shimoda, Masayuki;Takahashi, Meiko;Kubo, Hajime
目的：淋巴分化主控基因proxy在胎儿肝细胞迁移过程中也起着重要作用。在胚胎肝母细胞和成人肝细胞中均有表达。肝癌细胞在一定程度上与胚胎肝母细胞相似，因为它们都能增殖并侵入周围组织。为了解决Prox1可能参与肝细胞癌（HCC）肿瘤发生的可能性，对人类临床样本进行了分析。实验设计：筛选prox1作为潜在的抑癌基因，分析其在肝癌细胞系和人肝癌组织中的表达。通过在HCC细胞系中短暂过表达Prox1和通过RNA干扰抑制其表达来评估其生长赋予能力。结果：我们发现Prox1的表达与肿瘤的分化评分有显著的相关性。随后，我们还发现Prox1在肿瘤中的低表达与预后不良密切相关。通过RNA干扰特异性敲低Prox1可显著促进体外细胞生长，而过表达Prox1则可显著抑制体外细胞生长。结论：我们的研究结果表明Prox1参与了HCC的分化和进展，因此它可能是开发新的HCC诊断和治疗策略的候选基因。
Purpose: It has been shown that a lymphatic differentiation master gene, proxy also plays an essential role in fetal hepatocyte migration. Its expression is detected in embryonic hepatoblasts and in adult hepatocytes. Hepatoma cells are similar to embryonic hepatoblasts to a certain extent because they both proliferate and invade the surrounding tissue. To address the possibility that Prox1 may be involved in the tumorigenesis of hepatocellular carcinoma (HCC), human clinical samples were analyzed.Experimental Design: To screen prox1 as a potential tumor suppressor gene, its expression was analyzed in HCC cell lines and in human HCC tissues. Its growth-conferring abilities were assessed by transiently overexpressing Prox1 in HCC cell lines and by knocking down its expression by RNA interference.Results: We found that there was a significant correlation between Prox1 expression and the differentiation scores of the tumors. Subsequently, we also showed that low expression of Prox1 in tumors was closely associated with a poor prognosis. The specific knockdown of Prox1 by RNA interference strongly accelerated in vitro cell growth, whereas the overexpression of Prox1 greatly suppressed the growth.Conclusions: Our results suggest that Prox1 is involved in the differentiation and progression of HCC, and thus it may be a candidate for the development of novel diagnostic and therapeutic strategies for HCC.