Increased expression of focal adhesion kinase correlates with cellular proliferation and apoptosis during 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis
Increased expression of focal adhesion kinase correlates with cellular proliferation and apoptosis during 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis
复制标题
4-硝基喹啉-1-氧化物诱导大鼠舌癌过程中粘着斑激酶表达增加与细胞增殖和凋亡相关
DOI：
10.1111/j.1600-0714.2008.00728.x
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发表时间：
2009-07-01
影响因子：
3.3
通讯作者：
Cheng, Bin
中科院分区：
文献类型：
--
作者：
Xia, Juan;Lv, Na;Cheng, Bin
背景：口腔癌的发生是一个多步骤的过程，需要一系列分子遗传事件的积累和相互作用。粘着斑激酶（FAK）是一种非受体酪氨酸激酶，在整合素介导的细胞粘附位点和生长因子受体引发的信号传导途径中起重要作用。FAK的过表达与口腔鳞状细胞癌（OSCC）有关。方法：采用免疫组织化学方法检测4-硝基喹啉-1-氧化物诱导的大鼠舌鳞癌癌变过程中FAK蛋白表达、增殖细胞核抗原（PCNA）和凋亡细胞（TUNEL法）的变化。FAK免疫组化指数与PCNA标记指数呈正相关（r = 0.946，P < 0.05），而凋亡指数与最终FAK指数呈负相关（r =-0.959，P < 0.05）。抑制FAK可能是一种潜在的治疗策略。
Background:Oral carcinogenesis is a multistep process and requires accumulation and interplay of a series of molecular genetic events. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an important role in signalling pathways that are initiated at sites of integrin-mediated cell adhesions and by growth factor receptors. Overexpression of FAK has been linked to oral squamous cell carcinoma (OSCC). So, it is hypothesized that FAK expression might contribute to oral carcinogenesis.Methods:During 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis, FAK protein expression, proliferating cell nuclear antigen (PCNA) and apoptotic nuclei (TUNEL assay) were examined by means of immunohistochemistry.Results:Along with the progress of multistage carcinogenesis, FAK expression increased significantly among different histopathological groups with normal mucosa, mild-dysplastic epithelia, moderate-dysplastic epithelia, severe-dysplastic epithelia and in turn OSCC. Furthermore, FAK immunohistochemical index and PCNA-labelling index displayed positive correlation (r = 0.946, P < 0.05), while negative associations were revealed between apoptotic index and final FAK index (r = -0.959, P < 0.05).Conclusion:Our results implicated a role for FAK in oral carcinogenesis. Inhibition of FAK might be a potential novel treatment strategy in this disease.