調控第二型轉麩胺酶在肺癌細胞株表現的機制

Regulatory mechanism involved in transglutaminase 2 expression in lung cancer cells

趙育麟(Yu-Lin Chao)

指導教授 ： 李宜儒

中山醫學大學/醫學院/微生物免疫研究所/碩士(2013年)

摘要

第二型轉麩胺酶（transglutaminase 2；TG2）為一多功能蛋白，具有轉麩胺酶活性、G蛋白活性、雙硫異構酶活性以及蛋白質激酶活性。在細胞中主要位於細胞質，但是亦分佈於細胞核、細胞膜、細胞表面，甚至可以分泌到細胞外。位於細胞表面的第二型轉麩胺酶可與integrin作用，進而促進細胞黏附。近來的文獻更進一步指出第二型轉麩胺酶與癌細胞的轉移有關。在此，我們使用高轉移性肺癌細胞株CL1-5及低轉移性細胞株CL1-0去探討第二型轉麩胺酶在肺癌細胞轉移中所扮演的角色以及控制其表現之機制。我們的結果顯示，降低第二型轉麩胺酶的表現量，或者在細胞培養時加入第二型轉麩胺酶抗體CUB7402會抑制CL1-5的移行和侵入。然而，加入第二型轉麩胺酶活性抑制劑對CL1-5的侵入和移行能力沒有影響。因此，第二型轉麩胺酶對肺癌細胞移行和侵入能力可能受其數量或分布所影響，而與活性無關。第二型轉麩胺酶在CL1-0的表現量可以由同時處理5-Aza-2’-deoxycystidine and trichostatin A或是分別刺激過氧化氫或腫瘤壞死因子而提高。但是，第二型轉麩胺酶在CL1-5的表現量僅能些微地被pyrrolidine dithiocarbamate或genistein降低。

關鍵字

肺癌細胞株 ； 第二型轉麩胺酶轉移

並列摘要

Transglutaminase 2 (TG2) is a multifunctional protein, harboring transamidation, G protein, protein disulfide isomerase and protein kinase activities. It mainly localizes in the cytosol, but also distributes in the nucleus, cell membrane, cell surface, or even the exterior of the cell. Cell surface TG2 interacts with integrins, promoting cell adhesion. Recent findings further reveal the involvement of TG2 in tumor metastasis. Here, we further explore the role of TG2 in metastasis and the regulatory mechanism for TG2 expression using the highly metastatic lung cancer cell line CL1-5 and the low metastatic line CL1-0. Our results show that lowering TG2 expression or application of TG2 antibody (clone CUB7402) in cultures suppresses cell migration and invasion in CL1-5. However, inclusion of a TG2 inhibitor does not affect these events, suggesting that the amount or the distribution of TG2, but not the activity of TG2, play a role in tumor metastasis. Low expression levels of TG2 in CL1-0 are increased by the combined treatment of 5-Aza-2’-deoxycystidine and trichostatin A as well as either hydrogen peroxide or tumor necrosis factor-α, By contrast, expression of TG2 in CL1-5 is only slightly decreased by pyrrolidine dithiocarbamate and genistein.

並列關鍵字

lung cancer ； TG2 ； metastasis

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