γ-突触核蛋白在胰腺腺癌中的过表达。

Overexpression of synuclein-gamma in pancreatic adenocarcinoma.

作者信息

Li Zhongkui, Sclabas Guido M, Peng Bailu, Hess Kenneth R, Abbruzzese James L, Evans Douglas B, Chiao Paul J

机构信息

Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, PO Box 424, Houston, TX 77030, USA.

出版信息

Cancer. 2004 Jul 1;101(1):58-65. doi: 10.1002/cncr.20321.

DOI:10.1002/cncr.20321

PMID:15221989

Abstract

BACKGROUND

Currently, pancreatic adenocarcinoma is the fourth leading cause of cancer-related death in the United States. Despite the advances in pancreatic carcinoma research, patients with this devastating disease have a very poor prognosis. To identify the gene expression profile of pancreatic carcinoma, an important step in the process of developing new diagnostic and therapeutic strategies, the authors investigated the alteration of gene expression in this disease.

METHODS

The authors analyzed a public serial analysis of gene expression (SAGE) database and examined in greater detail the expression of synuclein-gamma mRNA in several pancreatic carcinoma cell lines and tumor tissue samples by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and Northern blot analysis. The expression of synuclein-gamma protein was investigated further by immunohistochemical and Western blot analyses using tumor cell lines, tumor tissue, and serum samples.

RESULTS

Synuclein-gamma mRNA was overexpressed in 11 of 12 pancreatic carcinoma cell lines, including AsPc-1, MDAPanc28, Capan-1, Capan-2, PANC-1, HS766T, MDAPanc3, MDAPanc48, Colo357FG, MiaPaCa2, CFPac1, and BxPc3. The expression of synuclein-gamma protein was detectable in 8 of 12 pancreatic carcinoma cell lines (67%) and in 22 of 32 pancreatic tumor tissue samples (69%) by Western blot analysis. On immunohistochemical staining, synuclein-gamma protein was present in 61% of the tumor tissue samples examined from patients with Stage I and II pancreatic carcinoma. The overexpression of synuclein-gamma is correlated with perineural and lymph node invasion. Synuclein-gamma protein also was detectable by Western blot in serum samples from 21 of 56 patients (38%) with pancreatic carcinoma.

CONCLUSIONS

Synuclein-gamma, which initially was described as a breast carcinoma-specific gene involved in invasion, metastasis, and chemotherapy resistance, was frequently overexpressed in pancreatic carcinoma. Overexpression of synuclein-gamma may play a role in pancreatic carcinoma invasion. Further studies will be necessary to determine the role of synuclein-gamma in pancreatic carcinoma.

摘要

背景

目前，胰腺腺癌是美国癌症相关死亡的第四大主要原因。尽管胰腺癌研究取得了进展，但患有这种毁灭性疾病的患者预后非常差。为了确定胰腺癌的基因表达谱，这是开发新的诊断和治疗策略过程中的重要一步，作者研究了该疾病中基因表达的变化。

方法

作者分析了一个公开的基因表达系列分析（SAGE）数据库，并通过逆转录聚合酶链反应（RT-PCR）分析和Northern印迹分析更详细地检测了几种胰腺癌细胞系和肿瘤组织样本中γ-突触核蛋白mRNA的表达。使用肿瘤细胞系、肿瘤组织和血清样本，通过免疫组织化学和蛋白质印迹分析进一步研究了γ-突触核蛋白的表达。

结果

γ-突触核蛋白mRNA在12个胰腺癌细胞系中的11个中过度表达，包括AsPc-1、MDAPanc28、Capan-1、Capan-2、PANC-1、HS766T、MDAPanc3、MDAPanc48、Colo357FG、MiaPaCa2、CFPac1和BxPc3。通过蛋白质印迹分析，在12个胰腺癌细胞系中的8个（67%）以及32个胰腺肿瘤组织样本中的22个（69%）中可检测到γ-突触核蛋白的表达。在免疫组织化学染色中，61%的来自I期和II期胰腺癌患者的肿瘤组织样本中存在γ-突触核蛋白。γ-突触核蛋白的过度表达与神经周围和淋巴结浸润相关。通过蛋白质印迹法在56例胰腺癌患者中的21例（38%）的血清样本中也可检测到γ-突触核蛋白。