腫瘤胚基因 (oncofetal gene) 係為表現於胚胎時期的基因，隨著發育為正常成體會降低表現或是不表現，而後當腫瘤形成時，其腫瘤胚基因又再次大量表現。一般較為人熟知的腫瘤胚基因有 α-fetoprotein (AFP)及 Glypican-3 (GPC3)，這類基因在肝癌上是很好的癌症診斷指標，基於這樣的概念，本實驗室從 Unigene、ORESTES 等資料庫中，建立屬於我們自己的資料庫，藉由這個資料庫，我們鎖定一個功能未知基因— LRRC16B (leucinerich repeat containing 16B)，將之命名為 Embryonic Gene Re-express in Tumor–Unknown 5 簡稱 EGRT-U5。藉由一連串的篩選，我們也確認了EGRT-U5具有類腫瘤胚基因的表現型。利用生物資訊軟體分析發現此未知蛋白之 N端具有 LRR domain，而 C端含有數個細胞核定位訊號 (NLS)，為了瞭解這兩個蛋白模組對EGRT-U5功能上的角色，我們將 EGRT-U5 分成兩段進行酵母菌雙雜合實驗，依序分別為具有LRR domain之U5 (1-991) 與含有 NLS 之U5 (991-1370) 。以酵母菌雙雜合實驗分析，找到4 個可能與U5 (1-991) 以及5 個可能與U5 (991-1370) 有交互作用的蛋白質，分別有-actin、Protein phosphatase 3 (PPP3)、c-Src以及importin α等。以免疫沉澱和免疫螢光染色確認篩選結果，我們發現EGRT-U5與c-Src有交互作用。而且，先前的實驗結果也顯示，EGRT-U5具有促進細胞增生以及腫瘤形成的能力，我們推測可能是由於與c-Src的交互作用而造成。此外我們也針對c-Src下游的訊息傳導路徑做初步探討，結果顯示JNK pathway表現以及磷酸化程度都有顯著性增加。總結目前的實驗結果，EGRT-U5在促進細胞生長以及腫瘤形成的過程中有其生物意義，作用機制可能藉由與c-Src交互作用而調控JNK pathway活化，進而導致細胞增生以及腫瘤形成。

Oncofetal proteins, such as alpha-fetoprotein (AFP) and glypican-3 (GPC-3), are proteins expressed in embryonic stage, down-regulated in adult normal tissues but re-expressed in tumors. Recent studies showed that these proteins may be useful in cancer diagnosis and prognosis. Previously, we found LRRC16B (EGRT-U5, Embryonic Gene Re-express in Tumor-Unknown 5) presenting oncofetal-like patterns that was expressed in many tumor and fetal tissues including liver and colon but down-regulated in normal and non-tumor tissues. According to the bioinformatics analysis, EGRT-U5 has several leucine rich repeats (LRR) in N-terminus and nuclear localization signals in C-terminus. A number of recent studies revealed that the LRR domains probably were related to protein–protein interactions and the protein containing LRR domain may be associated with many biologically important processes, morphology and dynamics of the cytoskeleton and early mammalian development. In order to further determine protein domains of EGRT-U5 which are responsible for interaction, we had cloned two truncated constructs pGBKT7-U5 (1-991) and pGBKT7-U5 (991-1370). By using these truncated constructs as baits, we screened a testis cDNA library to sift protein-protein interaction by yeast two-hybrid system. Presently, we found 4 proteins may interact with U5 (1-991) and 5 proteins may interact with U5 (991-1370), including beta-actin, Protein phosphatase 3 (PPP3), c-Src tyrosine kinase and importin alpha among others. Using immunoprecipitation and immunofluorescence to verify these results, we observed the EGRT-U5 could interact with c-Src. Combined with the data before, it revealed the ability of cell proliferation and tumor formation may associated with the interaction between EGRT-U5 and c-Src. Moreover, we also detected the c-Src downstream signaling pathway expression levels, only the JNK pathway showed the dramatic change. In conclusion, we suggested the oncofetal-like protein, LRRC16B (EGRT-U5) may play a role in tumorgenesis and medieated by its interaction with c-Src to regulate the JNK pathway which results in tumor formation.

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周靖恆，結合生物資訊的方法探討腫瘤相關基因在人類腎臟癌中的表現，國立成功大學分子醫學研究所碩士論文，民國九十四年。
吳宗樺，研究一個具有腫瘤胚胎表現型的功能未知基因-LRRC16B，國立成功大學分子醫學研究所碩士論文，民國九十六年。
林照蓉，研究一個具有腫瘤胚胎表現型的功能未知基因-LRRC16B，國立成功大學分子醫學研究所碩士論文，民國九十七年。