胰腺癌组织中Snail与E-钙黏素蛋白的表达及临床意义

Expression of Snail and E-cadheein in pancreatic carcinoma and clinical significance thereof

目的研究Snail在胰腺癌组织中的表达及其通过抑制E-钙黏素对胰腺癌侵袭性生物学行为的影响。方法采用免疫组织化学的方法检测了56例胰腺癌组织中Snail、E-钙黏素蛋白的表达,并与临床病理资料作对照分析,同时将Snail的编码基因导入胰腺癌细胞系Panc-1,观察其对胰腺癌细胞E-钙黏素的表达以及侵袭能力的影响情况。结果56例胰腺癌组织标本中20例Snail(36%)阳性,在伴有淋巴结转移(P=0.006)、远处转移(P=0.001)以及E-钙黏素表达降低(P=0.038)的病例中Snail阳性表达率较高。将Snail的编码基因导入Panc-1细胞之后可以明显抑制E-钙黏素的表达,同时促进细胞在体外的侵袭能力。结论Snail在胰腺癌中存在着重新表达的现象,Snail可能通过抑制E-钙黏素从而在胰腺癌的侵袭过程中发挥作用。

Objective To investigate the expression of Snail, a newly discovered inhibitory transcription factor, and E-cadherin in pancreatic carcinoma （PC） and clinical significance thereof. Methods Immunohistochemistry was used to examine the expression of Snail and E-cadherin in 56 specimens of PC obtained during operation. PC cells of the line of Panc-1 and transfected with pCMV-Tag2B- Snail, a eucaryotic expression vector coding Snail, so as to obtain a stable clone named Panc-1-Snail. RT- PCR was used to detect the mRNA expression of Snail gene in the Panc-1-Snail cells. Immunofluorescence technique and Western blotting were used to detect the expression of E-cadherin in the Pan-1-Snail cells. Transwell cell culture chamber method was used to examine the invasion ability of the Panc-1-and Panc-1- Snail cells. Results Twenty of the 56 PC specimens （36%） were positive in Snail, mainly located in the nuclei. Seventeen of the 20 Snail-positive PC specimens were with and 3 without lymph node metastasis （ P =0.006） ; and 7 of the 8 PC specimens with lymph node metastasis were Snail-positive and only 1 was Snail-negative （P = 0. 001 ）. Twenty-six PC specimens showed low expression of E-cadherin with remarkable heterogeneity. Of the 20 Snail-positive PC specimens 13 showed low expression of E-cadherin and only 7 showed normal expression of E-cadherin; and 13 of the 36 Snail-negative PC specimens showed low expression of E-cadherin （P = 0.038） . RT-PCR showed strong Snail mRNA expression in the Pan-1 cells. Both Western blotting and immunofluorescence technique showed the depression of E-cadherin expression. The Transwell chamber test showed that the number of penetrating Pan-1-Snail cells after 24-hour incubation was （ 174 ±8）/200X field of view, significantly greater than that of the Pan-1 cells [ （96 ±4）/200X field of view, P 〈 0.01 ]. Conclusion Re-expressed in PC and accelerating the invasion of PC through depressing E-cadherin expression, Snail may present a new marker for predicting the aggressiveness of PC.