Carelli Stephana, Zadra Giorgia, Vaira Valentina, Falleni Monica, Bottiglieri Luca, Nosotti Mario, Di Giulio Anna Maria, Gorio Alfredo, Bosari Silvano
Laboratory of Pharmacology, Department of Medicine, Surgery and Dentistry, University of Milan, Polo H. San Paolo, Milan, Italy.
Lung Cancer. 2006 Sep;53(3):263-71. doi: 10.1016/j.lungcan.2006.06.001. Epub 2006 Jul 13.
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase linked to the integrin and growth factor receptor-signalling pathways that regulates a number of the biological processes involved in neoplastic transformation, invasion and metastases, such as cell adhesion, migration and apoptosis. Its up-regulation might play a role in the tumourigenesis of invasive tumours, but its involvement in human lung cancer tissues has not yet been determined. We immunohistochemically compared FAK expression and localisation in 60 formalin-fixed and paraffin-embedded non-small cell lung cancer (NSCLC) tissues with that in the surrounding non-neoplastic tissue and in a further five microscopically normal lungs. FAK mRNA levels were quantitatively determined by real-time RT-PCR in frozen tissue specimens of all of the tumours and 21 matched non-neoplastic lung parenchymas, and protein expression in 16 homogenates of the matched neoplastic/non-neoplastic specimens was evaluated by Western blotting. The three different techniques showed that FAK is weakly expressed in non-neoplastic lung parenchyma and up-regulated in NSCLCs. Moreover, Western blotting and real-time RT-PCR indicated a statistically significant correlation between FAK up-regulation and higher disease stages (I+II versus III+IV, p=0.019 and 0.028, respectively). Our results provide evidence that FAK is up-regulated in NSCLCs, and suggest its potential involvement in lung cancer progression.
粘着斑激酶（FAK）是一种非受体酪氨酸激酶，与整合素和生长因子受体信号通路相关联，可调节肿瘤转化、侵袭和转移过程中涉及的许多生物学过程，如细胞粘附、迁移和凋亡。其上调可能在侵袭性肿瘤的发生中起作用，但其在人肺癌组织中的作用尚未确定。我们采用免疫组织化学方法，比较了60例福尔马林固定、石蜡包埋的非小细胞肺癌（NSCLC）组织中FAK的表达和定位与周围非肿瘤组织以及另外5例显微镜下正常肺组织中的情况。通过实时RT-PCR定量测定了所有肿瘤的冷冻组织标本以及21例匹配的非肿瘤性肺实质中FAK mRNA水平，并通过蛋白质印迹法评估了16例匹配的肿瘤/非肿瘤标本匀浆中的蛋白质表达。这三种不同技术显示，FAK在非肿瘤性肺实质中弱表达，在NSCLC中上调。此外，蛋白质印迹法和实时RT-PCR表明，FAK上调与更高的疾病分期（I+II期与III+IV期，分别为p=0.019和0.028）之间存在统计学显著相关性。我们的结果提供了证据表明FAK在NSCLC中上调，并提示其可能参与肺癌进展。
