腫瘤胚胎基因(Oncofetal Gene)是指在胚胎發育時期高度表現之基因，隨著個體年齡增長，其表現量降低或是不被表現。然而當個體患有惡性腫瘤時，腫瘤胚胎基因會再度被活化表達，而此一特性在臨床上能做為偵測癌症發生以及復發的指標。實驗室在先前已建立一套生物資訊系統，從表達序列標記片段(EST)資料庫中，尋找腫瘤胚胎候選基因，再藉由RT-PCR方式初步篩選出具有腫瘤胚胎表現型(Oncofetal Phenotype)基因進行研究。利用此生物資訊系統找出之Lin28B，已被證實為一個良好的循環腫瘤胚胎幹細胞標記(Circulating oncofetal tumor-stem-cell-like marker)，可辨識臨床檢體是否具有腫瘤幹細胞(Tumor stem cell)，並能針對病患進行轉移性復發及預後風險評估。
從上述生物資訊系統中找出另一個具有潛力之基因─C11orf41。C11orf41是一個已知核苷酸序列但生物功能未知的基因，經RT-PCR方式初步篩選後，發現在大多數腫瘤細胞株中均有表現，但僅在部分正常組織(胚胎時期腦部組織、成人腦部組織、睪丸和脊椎)中被偵測到，而在腫瘤-非腫瘤組織配對檢體中也有相似的結果，因此證實C11orf41為一個腫瘤胚胎基因。另外，在誘導性多功能幹細胞(iPS)及富有EpCAM (Stem Cell marker)之肝癌細胞中也能偵測到C11orf41的表現，進而提出C11orf41是一個具有潛力之腫瘤胚胎幹細胞標記的假設。
本篇研究首先構築C11orf41與EGFP及Myc epitope的融合蛋白，以反轉錄病毒感染方式建立Over-expressed C11orf41穩定細胞株，再藉由西方點墨法確認C11orf41蛋白質表現，並利用共軛焦顯微影像系統發現C11orf41會在細胞質中形成聚集蛋白(Aggregate Protein)。另外也建構了7 個C11orf41的截短蛋白(Truncated Protein)分別與EGFP及Myc epitope進行融合，以共軛焦顯微影像系統觀察，其中C11orf41(4519-5547b.p)和C11orf41(3988-5547b.p)在細胞核內會有聚集蛋白的形成。證明在C11orf41蛋白質C’端序列上除了具有聚集結構之外，可能還存在著核定位序列(NLS)，有助於C11orf41進入細胞核內參與基因之調控。因此，認為C11orf41可能是一個具有功能之蛋白質，但實際參與的作用機制仍待後續研究解謎。

Aim of the study was to validate the function of C11orf41 which was a potential oncofetal tumor-stem-cell marker. I have constructed the full-length of C11orf41 fused with EGFP or Myc epitope tag into pMSCV vector, and cloned 7 different truncated EGFP/ Myc epitope tag fusion proteins. To investigate the functions of C11orf41, Human HCC cell line, HepG2, was overexpressed C11orf41-EGFP by retrovirus infection and DNA transfection. The localization of C11orf41-EGFP fusion protein were accumulating on cell cytoplasm, and becoming insoluble in cells. In addition, COOH terminus proteins of C11orf41 were aggregated and translocated into nucleus. The study reveals that COOH terminus of C11orf41 may play an important role in protein’s function, but detailed mechanisms are still unknown.

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