Zeb1 and twist are more commonly expressed in metastatic than primary lung tumours and show inverse associations with claudins.
BACKGROUND
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.


OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Internal Medicine, Respiratory Research Unit, Clinical Research Center, Oulu University Hospital, Oulu, Finland.
Heta
H
Merikallio
Riitta
R
Kaarteenaho
Paavo
P
Pääkkö
Siri
S
Lehtonen
Pasi
P
Hirvikoski
Riitta
R
Mäkitaro
Terttu
T
Harju
Ylermi
Y
Soini
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D057167:Claudins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000556:secondary*; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1
D057167:Claudins; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1