The Expression Of RPS15a In Gastric Cancer And Its Roles In Stimulation Of The Growth Of Gastric Cancer Cells

【Background】Ribosome Protein S15a (RPS15a) is located on chromosome 16 (16p13) which belongs to RPS8 family. It has 7369 base pairs, encoding 130 amino acids with the molecular weight of 14.8 kDa. It was ever reported that ribosomal protein S15a could be upregulated by HBxAg.RPS15a accelerated hepatocellular growth in culture, soft agar, and also promoted tumor formation, suggesting that S15a overexpression may contribute to hepatocarcinogenesis. RPS15a was also differentially expressed in poorly differentiated DCIS and invasive stageⅢbreast cancers. The expression of RPS15a was downregulated in E2-Treated Androgen-Independent Prostate Cancer. RPS15a is a transforming growth factor beta(TGFb1) responsive gene that appears to promote cell proliferation in human lung carcinoma cell line A549. Adam et al found in Zebrafish that RPS15a was an oncogene. RPS15a has also been shown to interact with CaM. The results provide the basis for further investigation of how the binding of ribosomal proteins to Ca2+/CaM modulates ribosome assembly and/or the process of translation. RPS15a was upregulated by c-myc gene and downregulated by Krüppel-like factor 4. Taken together, RPS15a may play an important role in the development of cancer.【Objectives】To study the expression and significance of Ribosome Protein S15a (RPS15a) in gastric carcinoma tissues; To explored the effects of RPS15a protein on malignant biological behaviors of gastric cancer cells.【Methods】(1) SP immunohistochemistry was used to detect the expression of RPS15a protein in 100 samples of gastric carcinoma and the matched adjacent nonneoplastic tissues. (2) The expressions of RPS15a in gastric cancer cells and immortalized gastric epithelial cell line were measured by Western blot.(3) PcDNA3-RPS15a vector was transfected into gastric carcinoma cells, then screening and verifying were performed. (4) The growth of gastric carcinoma cells was tested by MTT assay; the cell cycle of gastric carcinoma cells was detected by flow cytometry. (5)Migration assay and invasion assay in vitro were used to determined the effect pcDNA3-RPS15a on the abilities of migration and invasion of gastric cancer cells.【Results】(1) In 100 samples of gastric carcinoma and the matched adjacent nonneoplastic tissues, the positive expression rate of RPS15a protein was 78.0% (78/100) and 44.0%(44/100) respectively. Statistical analysis suggested that the positive expression rate of RPS15a protein in gastric carcinoma tissues was significantly higher than that in the matched adjacent nonneoplastic tissues(χ2=24.3, P <0.05). The expression of RPS15a protein was closely correlated with the depth of invasion (χ2=7.87, P <0.05) and lymph node metastases (χ2=6.53, P<0.05). (2) RPS15a was positively expressed in four gastric carcinoma cell lines at protein level but significantly low-expressed in immortalized gastric epithelial cell line.(3) MTT assay showed that SGC7901-pcDNA3-RPS15a cells proliferated faster than SGC7901 and SGC7901-pcDNA3 cells on the fourth day( P <0.05). (4) Flow cytometry test showed that 14.7% of SGC7901 cells and 19.6% of SGC7901-pcDNA3 cells were in S-phase, whereas 30.6% of SGC7901-pcDNA3-RPS15a cells were in S-phase( P <0.05). (5) The abilites of migration and invasion in gastric cancer cells were increased .PcDNA3-RPS15a increased the abilites of migration(P<0.05)and invasion(P<0.05)in gastric cancer cells.【Conclusions】(1) The positive expression rate of RPS15a protein in the gastric carcinoma tissues was significantly higher than that the matched adjacent nonneoplastic tissues. The expression of RPS15a protein was significantly correlated with the depth of invasion and lymph node metastasis. (2) RPS15a could promote the growth of SGC7901. (3) Overexpression of RPS15a could promote cell cycle progression and enhance invasiveness.