人類的WWOX基因位於易斷裂的第16對染色體長臂(q arm)23.3-24.1的位置上。在於多數癌症研究當中，WWOX目前被認為是個腫瘤抑制基因。過去研究顯示癌症進展必需伴隨著血管新生(angiogenesis)。基底細胞癌(BCC)是人類中最常見的惡性腫瘤。過去我們發現在大量表現WOX1蛋白的異種移殖基底細胞癌腫瘤中，癌細胞生長以及血管新生的情形是被抑制的。因此，本研究主要探討究竟在於人類基底細胞癌細胞株中，WOX1蛋白的表現是否與血管新生有關。我們利用了西方墨點法和免疫組織化學染色法(IHC)來偵測鹼性纖維細胞生長因子(bFGF)的表現量。進一步利用酵素連結免疫吸附分析(ELISA)和雞胚絨毛尿囊膜(CAM)實驗，以及人類臍帶內皮細胞(HUVECs)血管生成(tube formation)實驗來探討血管新生的情形。實驗結果顯示，利用基因轉殖技術在人類基底細胞癌的細胞株中，使得WOX1蛋白大量表現，此時鹼性纖維細胞生長因子在細胞中所表現的量相對於對照組是比較低的。在動物實驗當中，鹼性纖維細胞生長因子在於大量表現WOX1蛋白的基底細胞癌的切片上，與對照組相比也是來的比較低的。利用了酵素連結免疫吸附分析測量培養基中鹼性纖維細胞生長因子的量，發現大量表現WOX1蛋白的實驗組所釋放鹼性纖維細胞生長因子的量相對於對照組是較低的。在雞胚絨毛尿囊膜實驗中，顯示處理大量表現WOX1蛋白基底細胞癌的上清液後，血管新生的情形會下降。在人類臍帶內皮細胞血管生成的實驗中，處理大量表現WOX1蛋白基底細胞癌的上清液16小時後，血管生成的情形會明顯下降。概括上述，WOX1可能經由抑制鹼性纖維細胞生長因子的形成進而抑制血管新生的能力。

The human WWOX gene is located on a fragile site on the chromosome 16q23.3-24.1. Previous studies propose that WWOX is considered a candidate tumor suppressor gene. Previous studied show that tumor growth is angiogenesis-dependent. Basal cell carcinoma (BCC) is the most common malignant skin neoplasm of humans. We have previously observed that both tumor progression and angiogenesis was downregulated in the xenograft BCC tumor which was overexpressed WOX1. Thus, the aim of this study is to investigate expression of WOX1 is related to angiognensis in basal cell carcinoma. We used western blotting and immunohistochemistry to examine the expression of bFGF, and further, we investigated angiogenesis with ELISA, chick embryo chorioallantoic membrane (CAM) assay, and HUVECs tube formation assay. The results showed that the level of bFGF expression was down-regulated in the WOX1 over-expressed BCC (BCC/WOX1) cells, compared with control (BCC/pEGFPC1). In the animal model, the immuno-intensity of bFGF in the BCC/WOX1 solid tumor is significantly decreased, compared with control (BCC/Scramble). The ELISA assay showed that the secretion of bFGF to extracellular space was down-regulated in the BCC/WOX1 cells. In the CAM assay, the stimulation of angiogenesis on the CAM was reduced after treating condition medium from BCC/WOX1 cells. The HUVECs tube formation in the matrigel was down-regulated after treating condition medium from BCC/WOX1 cells. All of the above, WOX1 might inhibit bFGF expression, and further, it inhibits angiogenesis in BCC cells.

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