Nuclear translocation of survivin in hepatocellular carcinoma: A key to cancer cell growth?
Nuclear translocation of survivin in hepatocellular carcinoma: A key to cancer cell growth?
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DOI：
10.1053/j.humpath.2003.07.016
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发表时间：
2003-11-01
期刊：
影响因子：
3.3
通讯作者：
Tarnawski, AS
中科院分区：
文献类型：
--
作者：
Moon, WS;Tarnawski, AS
Survivin是最近发现的一种抗凋亡蛋白，是细胞分裂的调节因子。其在肝癌和正常肝组织中的表达和定位尚未完全阐明。我们检测了47例肝细胞癌（HCC）和周围非恶性肝组织中survivin、Fas、增殖细胞核抗原（PCNA）和凋亡的表达。为了进一步确定survivin表达与细胞增殖和凋亡的关系，我们对同一肝癌标本进行了survivin和PCNA TUNEL双免疫染色。47例hcc中有35例（74%）survivin免疫染色阳性。35例survivin阳性HCC中，22例（63%）HCC细胞呈点状核染色，其余13例以细胞质染色为主。相反，非恶性肝细胞仅显示细胞质染色。与非恶性肝组织相比，HCC细胞的pna标记和凋亡指数明显升高（P < 0.001）。此外，survivin核阳性HCC标本的PCNA标记指数最高。除HepG2细胞系外，肝癌细胞中survivin的核定位与肿瘤细胞去分化相关。Survivin表达与细胞凋亡呈负相关，与Fas表达呈强相关（P = 0.01）。所有4种HCC细胞系均显示survivin表达和点状核定位。我们的研究结果表明，在静止的非恶性肝细胞中，survivin定位于细胞质以抑制细胞凋亡，并在HCC细胞中转运到细胞核中。综上所述，survivin从细胞质向细胞核的易位可能是HCC细胞增殖分化的重要调控机制。(C) 2003 Elsevier Inc.版权所有。
Survivin is a recently described anti-apoptosis protein and regulator of cell division. Its expression and localization in hepatocethdar carcinoma (HCC) and in normal liver tissue has not been fully elucidated. We examined the expression of survivin, Fas, proliferating cell nuclear antigen (PCNA), and apoptosis in 47 specimens of hepatocellular carcinoma (HCC) and surrounding nonmalignant hepatic tissues. To further determine the relationship between survivin expression and cell proliferation and apoptosis, we performed double immunostaining for survivin and PCNA TUNEL staining in the same HCC specimens. Positive immunostaining for survivin was present in 35 of 47 (74%) HCCs. Twenty-two of 35 survivin-positive HCCs (63%) showed punctate nuclear staining in HCC cells, and the remaining 13 showed predominant cytoplasmic staining. In contrast, nonmalignant hepatocytes showed only cytoplasmic staining. HCC cells had significantly higher PCNA-labeling and apoptotic indices compared with the case of nonmalignant hepatic tissue (P < 0.001). Furthermore, nucleus-positive HCC specimens for survivin showed the highest PCNA labeling index. The nuclear localization of survivin in HCC cells correlated with tumor cell de-differentiation with the exception of the HepG2 cell line. Survivin expression was inversely associated with apoptosis and was strongly associated with Fas expression (P = 0.01). All 4 HCC cell lines examined showed survivin expression and punctate nuclear localization. Our results indicate that survivin is localized to the cytoplasm in quiescent nonmalignant liver cells to suppress apoptosis and translocates into the nucleus in HCC cells. In conclusion, translocation of survivin from the cytoplasm to the nucleus may constitute an important regulatory mechanism for cell proliferation and differentiation in HCC. (C) 2003 Elsevier Inc. All rights reserved.