探索乳癌細胞週期之調控因子訊號

A study of cell cycle regulatory signal for breast cancer

林榮鑾(lin jung luan)

指導教授 ： 吳家樂

亞洲大學/資訊學院/生物資訊學系碩士班/碩士(2007年)

摘要

癌症成因可歸咎於細胞不斷的增生，因此研究癌症與細胞週期基因的調控機制，是探討癌症發生的重要工作。基因表達(Gene Expression)資料庫大量建置，使得我們可以運用電腦運算的方式來探索基因的調控機制。基於有相同基因表達行為的基因群，其功能也會有相似之構想，本論文嘗試透過生物資訊的方法，去尋找調控 cell cycle 之共同訊號。 根據Michael Whitfield, and Sherlock, (2002)等人的論文，分別對乳癌五群週期性表達基因的 promoter 與轉錄因子結合位置（TF-binding sites），作序列比對。根據比對結果發現R11007;G002664 (Q9NS56)及R11006;G002663 (Q9NS56)這兩個轉錄因子結合部位同時出現於五個group中；在個別的組別中KNSL6、PRIM1、MCM6、FANCA及FLJ20510等五個基因的 promoter 有三個以上的調控因子結合位置。這結果顯示轉錄因子結合部位有組合性的可能，另一方面藉由蛋白質資料庫的資訊，可以找出轉錄因子結合部位對應之調控因子蛋白，然後再從這些調控因子蛋白找出相互作用的蛋白質，這些相互作用的蛋白質可能扮演調控TF的角色。 最後此研究也發現乳癌基因中有高比率的基因是位於CpG islands 的1000 bp 之內(58/83，約70%)，顯示了乳癌基因與 CpG islands 的高度關連。

關鍵字

乳癌、細胞週期、promoter、調控因子、CpG island

並列摘要

It is known that the cause of cancer is highly related to the control of cell division, hence, understanding the regulation mechanisms of the cancer cell cycle genes thus become an important task in exploring the cause of cancer. Thanks to massive establishment of gene expression database, we can now make use of computerized calculation to explore gene regulation. Basically，organism has a group of genes which has the similar gene expression pattern could has similar function too. The purpose of this research is to identify the common regulation signals for the breast cancer cell cycle genes by in silico approach.
According to the research work by Whitfield et al. (2002), they classified the breast cancer cell cycle genes into five groups based on their gene expression level, cell cycle phases and proliferation states. The promoter sequences of these five groups of genes are pairwise compared with known transcription factor binding sites (TFBS) in order to identify inter-group and intra-group common regulation binding regions.
After sequence comparison, it is found that two TFBS exist among the five groups simultaneously，this result suggested the existence of common regulation among groups. On the other hand, it is found that five of the cell cycle related promoter sequences (KNSL6, KNSL6, PRIM1, MCM6, FANCA, FLJ20510) have at least three known TFBS, this indicated the possibility of identifying the combinatory features of binding regions. Furthermore, transcription factors associated with these TFBS, and their protein-protein interactions are retrieved for further study.
At last, the research also found out there is a rather significant correlation between breast cancer genes location and the CpG islands, that is, a high ration are located with 1000 bp of a CpG island (58/83, around 70%).

並列關鍵字

breast cancer, promoter, cell cycle, transcription factor, CpG island

參考文獻

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