Reelin 是位於人類染色體 7q22 的基因，為細胞外基質糖蛋白，作用在 ApoER2 和低密度蛋白受體(low-density lipoprotein receptors；LDL receptors)以啟動胚胎期腦神經網路分化的途徑與移動。目前的研究中，首先、利用 RT-PCR 與免疫組織化學分析（immunohisto-chemistry analysis；IHC）分析組織微陣列分析(tissue microarrays；TMA)確認在各種成人組織中 Reelin 的表達模式，支持 Reelin 在細胞架構下穩定表達和控制許多器官發育過程時的建構。第二、我們調查Reelin 在腫瘤生成時的表達狀態。發現在數種不同型的癌症中 Reelin
皆失去表達，在乳癌與大腸癌超過 80%以上。另一方面，我們研究指出懸浮型態的小細胞肺癌(small cell lung cancer；SCLC) 團塊高度保留Reelin 的表達，然而貼附型的非小細胞肺癌確較無此現象。這意味Reelin 表達也可能影響體外培養肺癌細胞的細胞培養型態與生長特性。我們的結果還顯示癌症中 Reelin 表達沉默是直接與 DNA 高度甲基化有關，因為腫瘤細胞株加入 5-aza-2-deoxycytidine 後 Reelin 甲基化解除重新表達 Reelin。
可顯示在分子基礎上癌症中 Reelin 的不活化，在乳癌與大腸癌中機率超過 80%可作為一個重要的腫瘤標誌。

The Reelin gene located on the human chromosome region 7q22, encodes an extracellular matrix glycoprotein, a ligand for ApoER2 and low-density lipoprotein receptors (LDL) Receptor, is required for mediating the correct positioning of neurons during embryonic brain development1. In the current study, first we applied RT-PCR and immunohistochemistry analysis (IHC) analysis on tissue microarrays (TMA) to verify the Reelin expression patterns in a variety of adult tissues, suggesting additional roles for Reelin in stabling the cyto-architecture and controlling the remodeling of many organs during development. Second, we report the Reelin expression status in tumorigenesis. We discover that the loss of Reelin expression is associated with multiple types of cancers, including more than 80% of both breast and colorectal cancers. Interestingly, our study also found suspension small cell lung cancer (SCLC) cell lines that grow as large aggregates retained high Reelin expression, whereas attached non small cell lung cancer cultures do not. That may imply the Reelin expression may be also associated with cell culture morphology and growth characteristics in the in vitro culture system for lung cancers. Our results here also demonstrated that epigenetic silencing of Reelin expression by DNA hypermethylation in tumors directly correlates with loss of Reelin expression in many cancers. Reelinmethylation was reversed and expression restored by treating tumor cell lines with the demethylating agent 5-aza-2-deoxycytidine. In conclusion, from the molecular basis of Reelingene inactivation in human cancer here, we propose that the Reelinvariation in more than 80% of breast and colorectal cancers makes it a significant novel tumor marker.

中文摘要 2
ABSTRACT 3
ABBREVIATIONS 5
INTRODUCTION 6
MATERIAS AND METHODS 9
RESULTS 12
DISCUSSION 12
FIGURE LEGENDS 12
REFERENCES 12

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