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標題: 53BP1在非小細胞肺癌中之表現型式
Expression Profile of 53BP1 in Non-Small Cell Lung Cancer
作者: 鄭佳曄
Cheng, Chia-Yeh
Contributors: 邱繡河;許美鈴
周寬基
中興大學
關鍵字: DNA damage response;double-strand breaks;53BP1;non-small cell lung cancer
DNA損傷反應;雙股螺旋斷裂;53BP1;非小細胞肺癌
日期: 2007
Issue Date: 2012-09-04 10:49:05 (UTC+8)
Publisher: 生物醫學研究所
摘要: 在真核生物中,p53 binding protein 1 (53BP1)是高保留性的DNA損傷監控系統蛋白質。53BP1具有兩個BRCT domains,許多參與DNA修復和DNA損傷訊息傳遞的蛋白質也都具有此功能性區域。發生DNA損傷後,53BP1會快速地移動到DNA雙股螺旋斷裂位置並形成明顯清晰的核焦點。53BP1對於啟動DNA損傷監控蛋白的活化和抑制癌化而言是相當重要的。53BP1有利於末端接合修復和重鏈基因轉換重組的進行。目前的研究推論53BP1有助於遏止基因的不穩定性,然而仍不清楚53BP1的作用機制。
在我們的研究中,53BP1 mRNA於6株肺癌細胞株中表現量差不多。Western Blot分析顯示7株肺癌細胞株都會表現53BP1。臨床分析上,大約60-70%肺癌病人會表現53BP1。值得一提的是,分子量較高的53BP1''在H226、MCF-7中表現量特別高。此外,經cisplatin處理後,53BP1''的表現量差異比53BP1顯著。因此,我們推論不同型式的53BP1具有不同的生物意義並且於癌化過程中扮演不同的角色。
The p53 binding protein 1 (53BP1) is a highly conserved DNA damage checkpoint protein in all eukaryotes. 53BP1 contains two BRCT domains, which are present in several proteins involved in DNA repair and DNA damage-signaling pathways. Upon DNA damage, 53BP1 rapidly relocalized to DNA double-strand breaks and forms discrete nuclear foci. It has been shown that 53BP1 is required for DNA damage checkpoint protein activation and tumor suppression. 53BP1 facilitates the end-joining repair and class-switch repair processes. Impaired function of DNA damage response gives rise to chromosomal instability that can result in tumorigenesis. Although the mechanism of 53BP1 has been proposed to prevent genomic instability and tumorigenesis, the detail is still unclear.
Our results showed that 53BP1 mRNA expression is nearly the same in 6 lung cancer cell lines. By western blot analysis, 53BP1 was expressed in 7 lung cancer cell lines. About 60-70% lung cancer tissue specimens expressed 53BP1 mRNA and protein. Interestingly, a high molecular weight protein-53BP1'' was highly expressed in H226 and MCF-7 cell lines. Furthermore, expression of 53BP1'' was markedly increased than 53BP1 after cisplatin treatment. Hence, our results suggest that the different forms of 53BP1 contain distinct biological significance and may play diverse role in tumorigenesis.
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