神經母細胞瘤是美國最常見的兒童顱外癌症。目前普遍認為神經母細胞瘤的發生原因，是交感神經系統在發育過程中，神經分化異常或細胞凋亡失常。RIN是三磷酸鳥糞嘌呤水解酶的一種，歸類於Ras家族並僅只表現於神經系統中。在老鼠細胞株中的研究發現RIN參與神經分化及細胞轉型，但目前RIN在人類神經母細胞瘤中的角色尚未了解。透過反轉錄聚合酶連鎖反應 (RT-PCR)及定量反轉錄聚合酶連鎖反應(qRT-PCR)，我發現RIN mRNA表現在SH-SY5Y及IMR32神經母細胞瘤細胞株中但並不表現在NB69神經母細胞株，在Gene Expression Omnibus (GEO)資料庫中也發現相對於SH-SY5Y，另有兩株人類神經母細胞瘤細胞株的RIN mRNA表現量很低。另外，利用聚合酶連鎖反應，在NB69細胞株中並無法偵測到RIN的基因，而在SH-SY5Y及IMR32細胞株中卻仍可偵測到RIN的基因，與反轉錄聚合酶連鎖反應的結果是一致的。令人驚訝的是，透過西方墨漬法，在測試的三株神經母細胞瘤皆無法測到RIN蛋白質的表現。基因轉殖細胞穩定表現wild type RIN (wtRIN), constitutively active RIN (caRIN)及dominant negative RIN (dnRIN)被建立並用以進行實驗。實驗結果指出RIN可能參與神經分化、細胞移動、生存、及p38磷酸化。更進一步的實驗需要進行以了解RIN在神經母細胞瘤的發展所扮演的角色。

Neuroblastoma is the most common extracranial tumor in childhood in America. Neuroblastoma is believed to be developed due to neuronal differentiation failure and improper apoptosis that occur during the development of the sympathetic nervous system. RIN, a small GTPase, is known to participate in neuronal differentiation at least in murine cell lines. RIN belongs to the Ras superfamily and is expressed exclusively in neurons. Currently, the role of RIN in human neuroblastoma is unclear. By RT-PCR and real-time RT-PCR, RIN mRNA was detectable in SH-SY5Y and IMR32, not in NB69 human neuroblastoma cell lines. Based on the Gene Expression Omnibus (GEO) database at NCBI, the level of RIN mRNA was also greatly reduced in two other human neuroblastoma cell lines relative to SH-SY5Y. After examination of the RIN gene by PCR, three exons were detected in SH-SY5Y and IMR32 cell lines and seven neuroblastoma patients, but not in NB69 cells. Surprisingly, none of the three test neuroblastoma cell lines displayed detectable RIN protein based on Western blot analysis. Stable transfectants expressed ectopic wild type RIN (wtRIN), constitutively active RIN (caRIN), and dominant negative RIN (dnRIN) were established. Studies performed in these stable transfectants revealed that RIN seems to participate in neuron-like differentiation, cell migration, cell survival and NGF-independent p38 phosphorylation. Further studies are needed to understand the role of RIN in neuroblastoma development.

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