臺灣博碩士論文加值系統

維甲類化合物又稱類視網酸(Retinoids)為具有誘導細胞分化之物質。類視網酸單獨
或合併其它試劑使用於治療白血病及頭頸部腫瘤有很好的療效。類視網酸於體外研究中亦
可抑制多種癌細胞株之生長，此生長抑制機制與其誘導細胞週期停滯、分化及細胞凋亡有
關。過去的研究發現類視網酸會抑制SC-M1胃癌細胞株之生長，因此最近本實驗室利用RNA
分示法(differential display)於SC-M1胃癌細胞中篩選到一新的基因，命名為類視網酸
誘導基因（一），(Retinoid-inducible gene 1, RIG1)。RIG1和腫瘤抑制基因
H-REV107-1之核甘酸序列有54%相似性，因此本研究進一步探討RIG1基因的生物功能為何
。首先利用半定量聚合酉每連鎖反應分析比較13對正常及癌組織中RIG1基因表現量。結果
發現9個癌組織RIG1基因表現量較鄰近正常組織多，此結果顯示癌組織中RIG1基因之降低
或失去表現並不常見。此外在TSGH9201胃癌細胞中利用基因轉殖技術大量表現RIG1-EGFP
融合蛋白，結果發現大量表現RIG1-EGFP融合蛋白之TSGH9201細胞呈現凋亡現象。再進一
步以基因微陣列顯色分析系統(Microarray)，發現RIG1-EGFP融合蛋白，可以誘導七種基
因表現並抑制一種基因的表現，而這些基因和抗氧化、誘導細胞分化及細胞凋亡有關。
RIG1-EGFP融合蛋白在TSGH9201細胞大量表現時，會導致抗氧化基因表現下降以及細胞凋
亡和DNA修補等之基因表現量的上升，因此RIG1-EGFP融合蛋白的表現可能和促進TSGH9201
細胞氧化作用以及導致細胞死亡之機制有關。

Retinoids are compounds with capability of inducing cellular differentiation. They are effective in the treatment of acute promyelocytic leukemia and head and neck squamous cell cancer when used alone or incombination with other agents. In vitro studies have shown that retinoids suppress the growth of several types of cancer cells through inducing cell cycle arrest, differentiation or apoptosis. Studies from our laboratory have demonstrated the growth suppressive activity of all-trans retinoid acid on SC-M1 human gastric cancer cells. Also, a novel Retinoid-Inducible Gene 1 (RIG1) was isolated from SC-M1 cells treated with all-trans retinoid acid using the technique of mRNA differential display. Nucleotide sequences of the RIG1 cDNA showed 54% homology to a tumor suppressor gene H-REV107-1. To further investigate the biological function of RIG1 gene, I hace first used the technique of semi-quantitatve polymerase chain reaction to analyze and compare expression of the RIG1 gene in 13 pairs of tumor and adjacent normal tissues. The results showed that all investigated tissues expressed the RIG1 gene. Also, nine tumor tissues (six from breast, two from liver and one from stomach) had an increase in the RIG1 mRNA levels compared with that of the adjacent tissues.
　Furthermore, effects of over-expressing the RIG1-EGFP fusion protein were analyzed in TSGH9201 gastric cancer cells. Cells with apoptotic-like morphology were increased in TSGH9201 cells transient expressed the RIG1-EGFP fusion protein for two days. Alternation in gene expression patterns was further analyzed using the technique of Microarray. Expression of RIG1-EGFP fusion protein for two days resulted in increasing expression of seven genes (Heme oxygenase 1, GADD153, hPMS2, APG5, MAD, CDC2 and UVRAG) and decreasing expression of the Glutathione peroxidase 2. These differentially regulated genes are involved in the process of antioxidation, cellular apoptosis and DNA repair. Therefore, overexpression of the RIG1 gene may enhance cellular apoptosis through inducing oxidative stress of TSGH9201 gastric cancer cells.