Jia Pifeng, Li Feng, Gu Weiting, Zhang Weifeng, Cai Yu
Department of Neurosurgery, RuiJin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PLoS One. 2017 Mar 14;12(3):e0173473. doi: 10.1371/journal.pone.0173473. eCollection 2017.
This current study tested expression and potential biological functions of Gab3 in human glioma. Gab3 mRNA and protein expression was significantly elevated in human glioma tissues and glioma cells. Its level was however low in normal brain tissues and primary human astrocytes. In both established (U251MG cell line) and primary human glioma cells, Gab3 knockdown by shRNA/siRNA significantly inhibited Akt activation and cell proliferation. Reversely, forced Gab3 overexpression in U251MG cells promoted Akt activation and cell proliferation. In vivo, the growth of U251MG tumors in nude mice was inhibited following expressing Gab3 shRNA. Akt activation in cancer tissues was also suppressed by Gab3 shRNA. Together, we conclude that Gab3 overexpression in human glioma mediates Akt activation and cancer cell proliferation.
本研究检测了Gab3在人类胶质瘤中的表达及潜在生物学功能。Gab3 mRNA和蛋白表达在人类胶质瘤组织和胶质瘤细胞中显著升高。然而，其在正常脑组织和原代人星形胶质细胞中的水平较低。在已建立的（U251MG细胞系）和原代人胶质瘤细胞中，通过shRNA/siRNA敲低Gab3可显著抑制Akt激活和细胞增殖。相反，在U251MG细胞中强制过表达Gab3可促进Akt激活和细胞增殖。在体内，表达Gab3 shRNA后，裸鼠体内U251MG肿瘤的生长受到抑制。Gab3 shRNA也抑制了癌组织中的Akt激活。我们共同得出结论，人类胶质瘤中Gab3的过表达介导了Akt激活和癌细胞增殖。
