探討CCAR1對於胃癌細胞生長、遷移、入侵能力之影響

Studying the involvement of CCAR1 in the growth, migration, and invasion of gastric cancer cells.

鄭螢瞳(Ying-Tung Cheng)

指導教授 ： 江明格

國立中正大學/理學院/生命科學系生物醫學研究所/碩士(2015年)

摘要

根據世界衛生組織 (WHO)在2012年的統計，所有癌症中胃癌的死亡率為第三名，全世界大約有950,000人得到胃癌，因胃癌而死亡則有723,000人。胃癌常好發在亞洲、南美洲、東歐這些地區，在台灣胃癌也是經常出現的疾病，根據衛福部在2012的統計，十大癌症死因中胃癌排名第七。胃癌的成因相當複雜，可能由飲食習慣、環境、生活方式、遺傳等因素造成，所以目前都還沒有確切的解答。Cell cycle and apoptosis regulator 1 (Ccar1)目前研究發現主要扮演Co-activator，能夠幫助細胞核受體(Nuclear receptor)吸引中介體複合物 (Mediator complex)，增加下游基因的表現，其中有研究發現Ccar1能夠與Wnt訊息傳遞路徑中的β-catenin有交互作用。然而Ccar1在胃癌中所扮演的角色，目前沒有太多研究，因此我們實驗室就利用shRNA的方式來降低胃癌細胞中CCAR1的表現，我們發現降低CCAR1表現會抑制胃癌細胞的生長、遷移及入侵的能力，進一步利用流式細胞儀進行細胞週期的分析，發現降低CCAR1表現會使胃癌細胞的sub-G1增加，這也表示細胞會有細胞凋亡 (apoptosis)的出現。此外我們也利用相同的方式降低胃癌細胞中的β-catenin的表現，也發現能夠去抑制胃癌細胞的生長，接著進一步將CCAR1及β-catenin一起在胃癌細胞中降低表現，也能夠去抑制細胞生長。我們將會持續的去研究CCAR1及β-catenin之間的關係，以及他們在胃癌中所扮演的角色。

關鍵字

Wnt/β-catenin 訊息傳遞路徑 ； CCAR1 ； 胃癌

並列摘要

According to 2012 World Health Organization report, gastric cancer was the world’s third leading cause of cancer mortality, it occurred in 950,000 people and caused 723,000 deaths. It occurs most commonly in East Asia, South America and Eastern Europe. In Taiwan, the incidence of gastric cancer is particularly high, and it’s the seventh leading cause of death in 2012. The cause of gastric cancer is multifactorial such as diet, lifestyle, genetic, socioeconomic and other factors contribute to gastric carcinogenesis. However the molecular mechanism leading to gastric cancer is still not fully understood. Cell cycle and apoptosis regulator 1 (Ccar1) has been shown to play the role as a coactivator of nuclear receptors (NRs) to recruit mediator complex, and it is also part of the Wnt/β-catenin signaling pathway. However, the role of Ccar1 in gastric cancer is still poorly understood. We utilized shRNA to knockdown Ccar1 in gastric cancer cells, and found that suppression of Ccar1 expression inhibited the growth, migration and invasion of gastric cancer cells. Flow cytometry showed that depletion of CCAR1 increased the sub-G1 population, indicating that reduction of CCAR1 in gastric cancer cells was able to cause apoptosis. In addition, we knockdown β-catenin, the regulator of Wnt target gene, and found that it is also required for the growth of gastric cancer cells. When the expression of CCAR1 and β-catenin were both down-regulated, the growth of gastric cancer cells was further suppressed. We will continue to elucidate the relationship between CCAR1 and β-catenin and their roles in the development of gastric cancer.

並列關鍵字

Wnt/β-catenin signaling pathway ； CCAR1 ； gastric cancer

參考文獻

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