口腔鳞状细胞癌中的鼠肉瘤病毒基因

Rat sarcoma virus gene in oral squamous cell carcinoma

在口腔鳞状细胞癌(OSCC)中,鼠肉瘤病毒基因(RAS)亚型哈维-RAS、柯尔斯顿-RAS和神经母细胞瘤-RAS的突变频率分别为11.2%(140/1 251)、4.5%(35/786)和0.3%(1/375)。RAS基因突变大多发生于第12、13和61位密码子,造成RAS蛋白处于不断激活状态。持续活化的RAS蛋白可不断激活迅速加速纤维肉瘤-促丝裂原激活蛋白激酶和磷脂酰肌醇-3-激酶-蛋白激酶B下游信号转导,从而使细胞异常增殖,最终导致细胞恶性转化。RAS蛋白及其下游信号分子是OSCC治疗的分子靶点。本文就OSCC中RAS基因突变、激活机制和治疗靶点等研究进展作一综述。

In oral squamous cell carcinoma（OSCC）, the mutation frequencies of subtype Harvey rat sarcoma virus（R,4S）, Kirsten RAS, and neuroblastoma RAS of the RAS gene are 11.2%（140/1 251）, 4.5%（35/786）, and 0.3%（1/375）, respectively. RAS mutations occur mostly in 12, 13, and 61 codon sites and consistently generate active RAS, which can activate and rapidly accelerate the fibrosarcoma-mitogen-activated protein kinase and phosphatidylinositol-3-kinase-protein kinase B downstream signaling pathways. In these pathways, cells undergo aberrant proliferation and differentiation that can lead to malignancy. Hence, RAS and downstream signaling molecules are molecular therapeutic targets in OSCC. This review focuses on the mutation, activation mechanism, and therapeutic target of RAS in OSCC.