CapG 是由348 個胺基酸所組成的蛋白，屬於gelsolin 家族且具有調節肌動蛋白之功能。CapG 可藉由與肌動蛋白絲結合去調節肌動蛋白細胞骨架之活動性，進而參與細胞傳遞、受體媒介的胞膜變形運動、胞吞及細胞移行等作用。目前已經知道在一些具有高度轉移潛能的癌症中CapG 會有過度表現的情形，例如在肺腺癌細胞株CL1-5 即是如此，此現象指出CapG 可能與細胞移行及侵襲能力的調控有相關性。DNA 甲基化是上位基因調控機制的其中一種方式，而許多人類癌症的產生與基因上甲基化狀況的改變相關，在本實驗中，我們發現轉移能力較低的CL1-0 細胞經氧胞苷酸(deoxycytidine) 的類似物5-aza-2-deoxycytidine (5-Aza-dC) 處理之後，透過抑制甲基轉移酶(DNA methyltransferase) 的作用，CAPG 的mRNA 表現有顯著增加之情形。因此我們提出假說，CAPG 所受的上位基因調控與肺癌的轉移有關。除此之外，CL 肺腺癌細胞株中CAPG 的表現量與甲基化程度呈現反比關係。我們進一步以軟體分析並預測活化蛋白-1 (activator protein 1; AP-1) 可能會與CAPG 啟動子中受甲基化調控的區域結合進而調控CAPG 的基因表現。此研究結果證實FosB 以及JunD 確實能夠與CAPG 啟動子中的AP-1 結合位置結合，而將FosB 以及JunD 大量表達也能促使CapG 蛋白表現量增加。除此之外，將整合素Integrin α6/β4 大量表達也可促使CapG 蛋白表現量增加，因此我們認為此AP-1 所媒介之CAPG轉錄表現或許與Integrin α6/β4 之訊號傳遞有關。此研究將提出在肺癌轉移的過程中CAPG 的表現會受甲基化調控之證據，而CAPG 啟動子具變動性甲基化調控之區位的甲基化程度，或許可以成為肺癌侵襲程度及進程之指標，而對肺癌之診斷、預防跟治療有相當大的助益。

CapG, a 348-amino acid gelsolin-family actin-modulating protein, can make important contributions to actin-driven motility by binding and capping actin filaments to further involve in cell signaling, receptor-mediated membrane ruffling, phagocytosis, and motility. It has been known that CapG is overexpressed in highly metastatic cancer cells such as CL1-5, a lung adenocarcinoma cell line, indicating that it may involve in the control of cell migration and invasion. DNA methylation is one of epigenetic regulation mechanisms and the methylation pattern is altered frequently in a wide variety of human cancers. Here we show that CL1-0, a low-metastatic lung cancer cell line, treated with 5-aza-2-deoxycytidine (5-AZA-dC) significantly increases CAPG mRNA. Therefore, we hypothesized that epigenetic regulation of CAPG expression is associated with lung cancer metastasis. The expression levels of CAPG are inversely correlated with its DNA methylation status in the lung cancer cell lines. Furthermore, the activator protein 1 (AP-1) was predicted may bind to the dynamic methylation-regulated region of CAPG promoter and regulate CAPG expression. We found that FosB and JunD are able to bind to the AP-1 site in the CAPG promoter region, and that both FosB and JunD overexpression lead to increased CapG expression. Additionally, we considered that AP-1-mediated CAPG expression may be related to Integrin α6/β4 signaling because Integrin α6/β4 overexpression elevated CapG expression. This study will provide evidence that DNA methylation regulates CAPG expression during cancer metastasis and the hypomethylated CAPG gene promoter may serve as an invasiveness and progression marker for lung cancer diagnosis, prevention, and treatment.

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