肝细胞生成素或部分肝切除对PC3/BTG2基因的快速诱导及其在肝细胞癌中的mRNA表达

Rapid induction of PC3/BTG2 gene by hepatopoietin or partial hepatectomy and its mRNA expression in hepatocellular carcinoma.

作者信息

Zhang Zhi-Min, Wang Ge, Chen Chuan, Yang Zhi-Xiang, Jin Feng, San Jin-Lu, Xu Wen, Li Qiong, Li Zeng-Peng, Wang Dong

机构信息

Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2009 Jun;8(3):288-93.

PMID:19502170

Abstract

BACKGROUND

The anti-proliferative gene, PC3 (pheoch-romocytoma cell 3)/BTG2 (B-cell translocation gene 2), is one of the early growth response genes and belongs to the BTG/Tob protein family. This study aimed to assess the effects of recombinant human hepatopoietin (HPO) and partial hepatectomy on rapidly induced expression of immediate-early genes and to investigate the expression of PC3/BTG2 mRNA in hepatocellular carcinoma (HCC) at different stages of progression.

METHODS

After a rat model of partial hepatectomy was established, we investigated gene expression within 1 hour after 2/3 partial hepatectomy by representational difference analysis and in a primary cultured hepatocyte system. The expression levels of PC3/BTG2 from liver tissues of the rat model were assessed by RT-PCR and Northern blotting. Meanwhile, the expression of BTG2 mRNA in a tissue microarray of HCC was determined by in situ hybridization.

RESULTS

The PC3/BTG2 gene was rapidly induced after 2/3 partial hepatectomy and its expression peaked within 1-2 hours after operation. HPO rapidly induced the expression of the genes c-fos, LRF-1, and PC3 in primary cultured rat hepatocytes, which might be one of the molecular mechanisms by which HPO stimulates hepatocyte proliferation. Positive BTG2 mRNA expression was detected in 71.19% (42/59) of the HCC samples and in 75% (3/4) of the normal liver tissue samples obtained from the region around the HCC tissues. PC3/BTG2 mRNA was located mainly in the cytoplasm of HCC cells and its expression was related to the degree of differentiation.

CONCLUSIONS

Recombinant human HPO and partial hepatectomy rapidly induce the expression of the PC3/BTG2 gene. PC3/BTG2 mRNA is highly expressed in HCC cells and its expression is related to the degree of cell differentiation. The abnormal expression of PC3/BTG2 is closely related to the genesis and development of HCC, so PC3/BTG2 may play an important role in these processes.

摘要

背景

抗增殖基因PC3（嗜铬细胞瘤细胞3）/BTG2（B细胞易位基因2）是早期生长反应基因之一，属于BTG/Tob蛋白家族。本研究旨在评估重组人肝细胞生成素（HPO）和部分肝切除对即刻早期基因快速诱导表达的影响，并研究PC3/BTG2 mRNA在肝细胞癌（HCC）不同进展阶段的表达情况。

方法

建立大鼠部分肝切除模型后，我们通过代表性差异分析在2/3部分肝切除后1小时内研究基因表达，并在原代培养肝细胞系统中进行研究。通过RT-PCR和Northern印迹法评估大鼠模型肝组织中PC3/BTG2的表达水平。同时，通过原位杂交测定HCC组织芯片中BTG2 mRNA的表达。

结果

2/3部分肝切除后PC3/BTG2基因迅速被诱导，其表达在术后1 - 2小时达到峰值。HPO在原代培养的大鼠肝细胞中迅速诱导c-fos、LRF-1和PC3基因的表达，这可能是HPO刺激肝细胞增殖的分子机制之一。在71.19%（42/59）的HCC样本和75%（3/4）从HCC组织周围区域获取的正常肝组织样本中检测到BTG2 mRNA阳性表达。PC3/BTG2 mRNA主要位于HCC细胞的细胞质中，其表达与分化程度相关。