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，其中分為：胚胎時期、成人正常時期、腫瘤時期這三群資料庫。為了想找尋有 oncofetal genes/protein特徵的基因，我們利用 α-fetoprotein(AFP) 的 EST expression profile 當閥值 (threshold) 篩選出69個基因，其中30個在文獻中有較多的研究，另外39個基因在功能上則屬於未知的情況。之前本實驗室以 RT-PCR 的方式針對這69個基因做篩選驗證的結果中，我們鎖定一個功能未知基因— LRRC16B (leucine rich repeat containing 16B) 針對它做功能性探討 (Functional study)，為了研究方便，我們將此一基因暫時命名為 Embryonic Gene Re-express in Tumor–Unknown 5 (EGRT-U5)，簡稱為 U5。 RT-PCR 篩選結果發現EGRT-U5 幾乎在不同腫瘤細胞株都有表現，而正常成人組織除了在 bone marrow、brain 與 testis 等器官中表現比較顯著，其餘組織相較之下，表現量明顯低許多，此外在胎兒各器官組織皆可觀察到其表現。而偵測多種人類腫瘤，如乳癌、卵巢癌、肺癌等，整體來說在腫瘤組織中，EGRT-U5 表現量較非腫瘤組織高。
利用生物資訊軟體分析發現此未知蛋白之 N-terminal 具有 LRR domain，而 C-terminal 利用 PSORT II 與 motif scan 則預測出含有數個細胞核定位訊號 (NLS)，因此為了研究方便，將 EGRT-U5 分成三段來討論，依序分別為全長、具有 LRR domain 之一、二段與預測出含有 NLS之第三段。首先我們將全長以及其 truncated forms 與綠色螢光蛋白(EGFP) 作融合，得到EGRT-U5-full-EGFP、EGRT-U5-1.2-EGFP和EGRT-U5-3-EGFP 構築質體，運用短暫性轉染與篩選穩定表現 EGRT-U5 與 truncated forms 之 HEK293T 細胞群（stable pool）來作以下功能性探討，首先利用螢光顯微鏡觀察分佈情形，結果發現EGRT-U5-full-EGFP與EGRT-U5-1.2-EGFP融合蛋白主要分布於細胞質，偶而會聚集於細胞膜上，而 EGRT-U5-3-EGFP 融合蛋白則明顯分布於細胞核內。此外我們發現穩定表現EGRT-U5-full-EGFP與EGRT-U5-3-EGFP之HEK293T 細胞群，細胞型態明顯由人類腎臟上皮細胞的型態轉變為狹長狀。在細胞生長的實驗上結果顯示穩定表現EGRT-U5 全長與第三段之HEK293T 細胞群相對於對照組而言生長速率增加，其中穩定表現 EGRT-U5-3-EGFP 之 HEK293T 細胞群生長速率更加顯著。除了過度表現，還利用核糖核酸干擾技術 (RNAi)，短暫性轉染shRNA抑制穩定表現EGRT-U5全長與第三段之HEK293T 細胞群，實驗結果顯示其生長速率降低，然而抑制內生性 EGRT-U5 表現量最多之卵巢腫瘤細胞株— BG-1，短暫性轉染 shRNA 72小時後對細胞增長只有些微抑制，並不顯著。由西方墨點法實驗中發現此蛋白似乎具有insoluble 之特性。此外由於經由生物軟體預測出 EGRT-U5 第三段含有數個細胞核定位訊號，因此本實驗亦對 EGRT-U5-3-EGFP 融合蛋白入核機制利用定點突變做了一些探討，但是尚未找到可能之細胞核定位訊號。所以EGRT-U5目前發現在扮演細胞生長的角色上似乎佔有一席之地，而在未來可以更深入的研究此基因在癌症發生上所扮演的角色為何。

Oncofetal proteins, such as α-fetoprotein (AFP) and IMP-1, are proteins that are expressed in embryonic stage, down-regulated in adult normal stage, but re-expressed in tumors. These proteins are useful in cancer diagnosis and follow-up. Previously, we set up a bioinformatic program-Xcrunch to find candidate genes with potential oncofetal expression patterns. To confirm this finding, the candidate genes were screened for their expression in cancer cell lines, normal tissues, tumor tissues and rat tissues. We also collected some human tumor/ non-tumor tissues derived from kinds of organs such as breast, lung, ovary, kidney, liver and uterus to carry on gene analysis we collect several organs of different developmental stages from embryonic, newborn, and adult rats, respectively. One of the genes, LRRC16B (EGRT-U5, Embryonic Gene Re-express in Tumor-Unknown 5), was found to be up-regulated in many tumors and have an oncofetal-like expression pattern. LRRC16B (EGRT-U5) is a functionally unknown gene with several leucine rich repeats(LRRs) and nuclear localization signals.
In order to study the functions of EGRT-U5, we had cloned the full-length cDNA along with several truncated constructs— U5-full-length-EGFP and U5-3-EGFP. We had established the HEK293T pool stably expressing EGRT-U5-full-length and its truncated fusion protein. The western blot experiments were being carried out to confirm these constructs and we found EGRT-U5-full-length fusion protein had some insoluble property in transient transfection experiments. Overexpression experiments using those constructs were undertaken. After transfecting these constructs into HEK293T cells, the green fluorescent signal showed that the U5-full-length-EGFP fusion proteins are present diffusely in the cytosol, accenturated at the cell membrane, and forming dot-like structures in the nucleus, however, U5-3-EGFP fusion proteins were predominantly localized to the nuclei. Interestingly, in a HEK293T pool stably expressing U5-3-EGFP fusion proteins caused significantly morphology change. Moreover, overexpression of U5-full-length-EGFP and U5-3-EGFP significantly increased the growth of HEK293T cells as compared to that of expressing vector-alone cells by XTT assay. To investigate whether EGRT-U5 affected cell survival, we performed colony formation assay. EGRT-U5 overexpression in a HEK293T pool stably expressing U5-full-length-EGFP fusion proteins resulted in a increased colonogenicity. In addition, shRNA transient transfection was performed on ovary and liver cancer lines to knockdown EGRT-U5 and slightly suppressed the proliferation 72hr post transfection in ovary cancer line. In summary, our findings suggested EGRT-U5 might play important roles in tumorgenesis.

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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，國立成功大學分子醫學研究所碩士論文，民國九十六年。