The overexpression of polycomb group proteins Bmi1 and EZH2 is associated with the progression and aggressive biological behavior of hepatocellular carcinoma
The overexpression of polycomb group proteins Bmi1 and EZH2 is associated with the progression and aggressive biological behavior of hepatocellular carcinoma
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DOI：
10.1038/labinvest.2008.52
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发表时间：
2008-08-01
影响因子：
5
通讯作者：
Nakanuma, Yasuni
中科院分区：
文献类型：
--
作者：
Sasaki, Motoko;Ikeda, Hiroko;Nakanuma, Yasuni
多梳组蛋白Bmi 1和EZH 2参与了几种人类癌症的恶性转化和生物侵袭性。我们在此研究了Bmi 1和EZH 2在肝细胞癌（HCC）及其癌前病变、异型增生结节中的表达意义。采用免疫组织化学方法检测了Bmi 1和EZH 2在肝癌（n = 27）、异型增生结节（n = 14）以及肝细胞癌和胆管癌联合（HC-CC）（n = 14）中的表达。使用siRNA在培养的HCC细胞（HuH 7和HepG 2）中检查Bmi 1和EZH 2敲低的效果。经测定，Bmi 1在胆管细胞中持续表达，但在肝细胞中不表达，并且在胆管细胞和肝细胞中均未检测到EZH 2。Bmi 1和EZH 2在HCC中呈高表达，在HC-CC中表达更强（P < 0.01）。有趣的是，Bmi 1和EZH 2在异型增生结节中没有过表达。Bmi 1和EZH 2在HCC和HC-CC中的表达是异质性的，并与血管浸润、组织学分级和细胞增殖活性相关。在培养的过表达Bmi 1和EZH 2的癌细胞中，敲低Bmi 1和EZH 2导致细胞增殖活性降低。因此，多梳组蛋白Bmi 1和EZH 2的过表达与HCC的恶性进展相关，从而反映了HCC和HC-CC的侵袭性生物学行为。
Polycomb-group proteins Bmi1 and EZH2 are involved in the malignant transformation and biological aggressiveness of several human carcinomas. We herein examined the significance of the Bmi1 and EZH2 expression in hepatocellular carcinoma (HCC) and its preneoplastic lesions, dysplastic nodules. The expression of Bmi1 and EZH2 were examined immunohistochemically in HCC (n = 27) and dysplastic nodules (n = 14), and combined hepatocellular and cholangiocarcinoma (HC-CC) (n = 14). The effect of Bmi1 and EZH2 knockdown was examined in cultured HCC cells (HuH7 and HepG2) using siRNA. It was determined that Bmi1 was constantly expressed in cholangiocytes, but not in hepatocytes, and EZH2 was detected in neither cholangiocytes nor hepatocytes. Bmi1 and EZH2 were overexpressed in HCC and more extensively in HC-CC (P < 0.01). Interestingly, Bmi1 and EZH2 were not overexpressed in the dysplastic nodules. The expression of Bmi1 and EZH2 was heterogeneous and associated with vascular infiltration, the histological grades, and the cell proliferation activity in HCC and HC-CC. In cultured carcinoma cells overexpressing Bmi1 and EZH2, knockdown of Bmi1 and EZH2 resulted in decreased cell proliferation activities. Therefore, the overexpression of polycomb-group proteins Bmi1 and EZH2 is associated with the malignant progression of HCC, thereby reflecting the aggressive biological behavior in HCC and HC-CC.