LECT2分子量大小約16 kDa；是由人類T細胞白血病的細胞株(SKW-3)，在培養過程中加入PHA刺激後，由培養皿中的上清液所分離出來的。 LECT2在最近的研究中指出，在人類體內LECT2是由肝臟所合成的，且與細胞生長和修復有相關性。除了調控Wnt途徑之外，LECT2也參與中性球的化學趨化和刺激軟骨細胞的生長，或與類風濕性關節炎有相關性。此外在演化過程中LECT2是高度保留的基因，在細胞中扮演一個抑制Wnt/β-catenin訊號路徑的角色。而在肝臟致癌的過程中最常牽連到Wnt/β-catenin路徑。LECT2結抗肝臟腫瘤的作用及確切的機轉至今仍未完全釐清。因此，當LECT2過度的表現時，是否會經由抑制細胞中Wnt路徑的機轉來減弱癌細胞的致癌能力呢? 在初步的結果中發現，藉由腺病毒感染之後，細胞中大量表現LECT2有效的抑制細胞致癌的能力，例如:癌細胞的移動能力、侵襲能力和群落聚集的能力，還有影響肝臟癌細胞的細胞週期。另外在原位性肝癌動物實驗中，在基因治療後顯著的抑制惡性肝臟腫瘤的生長。總之當基因傳送使細胞內大量表現LECT2蛋白，這時有效減弱肝癌細胞的致癌能力，可能是藉由抑制Wnt/β-catenin訊號路徑，此外在動物實驗中也證實經基因治療後有效的抑制肝臟腫瘤的生長。所以在肝臟癌變過程中使LECT2大量表現或許可成為一個新的治療指標。

Leukocyte cell-derived chemotaxin 2 (LECT2) is first isolated as a 16-kDa secreted protein from cultured fluid of phytohemagglutinin-activated human T-cell leukemia SKW-3 cells. Recently LECT2 has shown to be synthesized by human hepatocytes and stimulates the growth of chondrocytes. LECT2 is involved in chemotactic factor to neutrophils and may be associated with rheumatoid arthritis. Besides, LECT2 is evolutionarily conserved and acts as a repressor in the Wnt/β-catenin signaling pathway. Wnt/β-catenin signaling is implicated in liver carcinogenesis. However, the exact roles of LECT2 in liver carcinogenesis are not yet well characterized. This study is to investigate the extra roles of LECT2 in Wnt signaling. Our results showed that adenoviral administration of LECT2 over-expression suppress oncogenic processes such as migration, invasion, proliferation and colony formation, as well as alteration in cell cycle distributions. In animal model significantly suppress liver malignancies in orthotopic Novikoff hepatoma. In conclusion, we show that ad-LECT2 gene delivery attenuated cell carcinogenesis process via downregulated Wnt/β-catenin signaling in vitro and suppressed tumor growth in vivo. Besides LECT2 over-expression represents a novel therapeutically factor for hepatocelluar carcinoma.

Abstract in Chinese.....................................01
Abstract in English......................................02
Abbreviations................................................03
Introduction...................................................04
Specific Aims................................................11
Experimental methods and material........12
Results...........................................................25
Discussion....................................................33
Figure and legends.....................................37
References...................................................55

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