| Summary: | 碩士 === 國立成功大學 === 微生物及免疫學研究所 === 94 === Epithelial membrane protein-2 (EMP2), a member of GAS3/PMP22 family, is a tetraspan protein and has been implicated in the control of cell growth, proliferation and cell apoptosis. Dr. N. H. Chow’s study revealed that soy isoflavones could enhance the expression level of EMP2 and inhibited the growth of bladder cancer cells. Besides, in microarray data EMP2 overexpression inhibited Ras related genes, such as Ras homolog gene family, member Q (RHOQ)、member of Ras oncogene family-like 4 (RABL4)、Ras and Rab interactor 3 (RIN3)。Ha-ras mutations are common in bladder carcinomas. It is interesting to reveal whether EMP2 overexpression can inhibit Ras related tumor formation. pEMP2-GFP fusion plasmid was transfected into Ras inducible cell line (7-4) to establish the stable cell lines. The results of the stable cell lines overexpressing EMP2 demonstrated that EMP2 can inhibit Ras activity as well as Ras protein expression and the regulation is at post-transcription level. EMP2 overexpression suppressed Ras induced cell proliferation but not cell migration. Further analysis showed that EMP2 overexpresion can induce cell apoptosis through disruption of the cell cycle progression. EMP overexpression could also suppress Ras induced colony formation. The EMP2 overexpression cells and 7-4 cells were subcutaneously injected into ICR and SCID mice, which are immune competent and immune deficient, respectively. For tumor formation, the tumor size in ICR and SCID mice was 6~27 fold and 3 fold smaller than the control Ras alone induced tumor. These results suggest that EMP2 can inhibit Ras induced tumor formation in mice and host immunity is also involved. Moreover, EMP2 overexpression can inhibit blood vessel formation. All toghther, we reveal that EMP2 overexpression inhibits Ras-related tumorigenesis, possibly through suppressing Ras activity, inducing cell apoptosis and decreasing blood vessels. In conclusion, EMP2 possesses features of tumor suppresser and has the potential to be used to against Ras-related cancers.
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