The variable expression of claudins in histologically different lung tumor types may be related partly to the cell type it originates from [83] . On the other hand, several growth factors and integrins modify claudin expression and they expression may vary in different types of lung tumors. EGF, for instance, inhibits claudin 2 expression while simultaneously increasing claudin 1, 3 and 4 expression and the transepithelial resistance without affecting the levels of occludin or ZO-1 in canine kidney cells [87] . In pneumocytes EGF upregulates claudins 4 and 7 while 3 and 5 are decreased [25] . Activating EGFR mutations are known to exist in nonsmall cell lung carcinoma and especially in adenocarcinoma and bronchioloalveolar carcinoma [88] . In line with this, claudins 1 and 4 show a high expression in lung adenocarcinomas and bronchioloalveolar carcinomas and claudin 2 and 5 are lower [40, 82] . Small cell lung carcinomas also display a higher expression of claudin 2 than adenocarcinomas [83] . Another mutation common to lung cancer is K-Ras [88] . Such mutations are present 15-30% of non small cell carcinomas [88] . In kidney cells, overexpression of ras leads to claudin 1, 4 and 7 overexpression while claudin 2 decreases and claudins 3 and 5 remain the same [89] . Similarly, some non-small cell carcinomas have PTEN (phosphatase and tensin homologue) mutations [90] . Inactivation or mutations of PTEN leads to activation of PKB (Protein kinase B) resulting in increased cell proliferation and inhibition of apoptosis [91] . Knockdown of PTEN has been shown to lead to a loss of polarization in colon carcinoma cells and strong downregulation of claudins 1, 3, 4 and 8 [92] . Small cell carcinomas and large cell neuroendocrine carcinomas, however, express c-kit, and they harbor c-myc amplifications and p53 and ras mutations, and loss of p16 and RB expression and their influence on claudin expression is not known [93] . Additional, several cytokines influence claudin expression and barrier function of epithelial cells and may surely influence also the expression of claudins in lung carcinomas [47] .