Department of Internal Medicine, Respiratory Research Unit, Clinical Research Center, Oulu University Hospital, Oulu, Finland.
J Clin Pathol. 2011 Feb;64(2):136-40. doi: 10.1136/jcp.2010.086678. Epub 2010 Dec 2.
Zeb1 and twist regulate expression of genes which take part in epitheliomesenchymal transition (EMT). Claudins are tight junctional proteins regulating polarity and paracellular permeability of epithelial cells.
To study Zeb1 and twist in 289 primary and 54 metastatic lung tumours and their relation to expression of claudins 1-5 and 7 by immunohistochemistry.
Metastatic tumours showed a significantly lower expression of zeb1 and twist (33.0% and 38.0% vs 5.0% and 14.5%, p<0.001 for both) and they also had a significantly lower expression of claudin 1 (p<0.001), claudin 4 (p<0.001), claudin 5 (p=0.001) and claudin 7 (p<0.001) than did primary tumours. Primary lung tumours showed a strong inverse association between zeb1 and claudin 1 (p=0.024) and claudin 2 (p=0.003). For twist an inverse association was found with claudin 5 (p=0.007). In metastatic tumours zeb1 was inversely associated with claudin 7 (p=0.050) and twist with claudin 5 (p=0.025). Overexpression of claudin 5 was associated with decreased survival (p=0.017). For zeb1 or twist, no association with survival was observed in primary or metastatic tumours.
According to protein expression, involvement of zeb1 and twist in EMT in primary lung tumours is relatively infrequent. Carcinomas metastatic to the lung showed a significantly higher expression of these transcriptional factors than primary lung tumours, indicating their probable importance in the metastatic process. Zeb1 and twist were inversely associated with several claudins, indicating a role in their down-regulation.
Zeb1 和 twist 调节参与上皮间质转化 (EMT) 的基因表达。 Claudin 是紧密连接蛋白，调节上皮细胞的极性和细胞旁通透性。
通过免疫组织化学研究 289 例原发和 54 例转移性肺肿瘤中 Zeb1 和 twist 的表达及其与 Claudin 1-5 和 7 的关系。
转移性肿瘤 Zeb1 和 twist 的表达显著降低（分别为 33.0%和 38.0%比 5.0%和 14.5%，均 p<0.001）， Claudin 1（p<0.001）、Claudin 4（p<0.001）、Claudin 5（p=0.001）和 Claudin 7（p<0.001）的表达也显著降低。原发性肺肿瘤 Zeb1 与 Claudin 1（p=0.024）和 Claudin 2（p=0.003）呈强负相关。 Twist 与 Claudin 5 呈负相关（p=0.007）。在转移性肿瘤中，Zeb1 与 Claudin 7（p=0.050）呈负相关，而 twist 与 Claudin 5（p=0.025）呈负相关。 Claudin 5 的过表达与生存率降低相关（p=0.017）。对于 Zeb1 或 twist，在原发性或转移性肿瘤中均未观察到与生存率相关的关联。
根据蛋白表达，Zeb1 和 twist 参与原发性肺肿瘤 EMT 的情况相对较少。转移到肺部的癌瘤显示出这些转录因子的表达明显高于原发性肺肿瘤，表明它们在转移过程中的重要性。Zeb1 和 twist 与几种 Claudin 呈负相关，表明它们在下调中的作用。
