SHP-2野生型基因可促进乳腺癌转移而其突变型基因可抑制转移

The wild-type SHP-2 gene promotes but the mutated SHP-2 gene inhibits the metastasis of breast cancer

目的:探讨含2个Src同源区2的蛋白酪氨酸磷酸酶(Src homology 2 domain-containing tyrosine phosphatase,SHP-2)在乳腺癌MCF-7细胞体内外移动和转移中的作用。方法:首先构建重组质粒SHP-2-绿色荧光蛋白(green fluorescent protein,GFP)基因及SHP-2C>S-GFP(SHP-2突变体),并分别转入乳腺癌MCF-7细胞中,建立2种细胞,即SHP-2-GFP-MCF-7和SHP-2C>S-MCF-7。利用荧光显微镜技术观察细胞移动情况,动物实验观察不同细胞移植组裸小鼠的肿瘤生长情况,从而确定蛋白酪氨酸磷酸酶SHP-2在乳腺癌细胞移动、侵袭和转移中的作用。结果:SHP-2转染的乳腺癌MCF-7细胞的体外移动能力增强,且在注射此组细胞的裸鼠中有肿瘤生长;而转染了SHP-2C>S-GFP的乳腺癌MCF-7细胞的移动能力明显减弱,且注射此组细胞的裸鼠未发现肿瘤生长。结论:SHP-2可促进乳腺癌MCF-7细胞在体外的移动及体内的侵袭和转移。

Objective： To investigate the role of SHP-2 [ a non-transmembrane type protein tyrosine phosphatase （PTPase） containing two SRC homology 2 （SH2） domains] in the invasion and metastasis of the breast cancer cell line MCF-7 in vitro and in vivo. Methods： This study constructed recombinant plasmid SHP-2-green fluorescence protein （GFP） （SHP-2-GFP） and SHP-2C 〉 S-GFP, respectively. The two plasmids were transfected into breast cancer MCF-7 cells to establish two cancer cell lines： SHP-2-GFP-MCF-7 cells and SHP-2C 〉 S-GFP-MCF-7 cells. The cell migration was detected by fluorescence microscopy and the growth of the different xenografted tumors in nude mice was observed. Results： The SHP-2-GFP-MCF-7 cell lines showed a higher cell migration ability, and tumor growth was observed in the nude mice after injection of SHP-2-GFP-MCF-7 ceils ; migration ability of MCFo7 cells was significantly weakened after transfection of recombinant plasmid SHP-2C 〉 S-GFP and no tumor growth was observed in the nude mice after injection of SHP-2C 〉 S-GFP-MCF-7 ceils. Conclusion：The tyrosine phophatase SHP-2 could promote the invasion and metastasis of the breast cancer cell line MCF-7 in vitro and in vivo.