title: Expression of desmogleins 1-3 and their clinical impacts on human lung cancer.
abstract: OBJECTIVE
  Desmogleins (DSGs) are components of the cell-cell connecting desmosomes. Desmosomal proteins have been found dysregulated in various cancers. Here we studied the role of DSGs in human lung cancer.
  
  
  METHODS
  Expression of DSG1-3 mRNA in lung cancer cell lines and human bronchial epithelial cells (HBEC) was examined by real time RT-PCR. Methylation status of DSG1-2 was evaluated by demethylation test and bisulfite sequencing (BS). Moreover, DSG1-3 protein expression was analysed in 112 primary lung tumor samples by immunohistochemistry (IHC) on tissue microarrays.
  
  
  RESULTS
  It turned out that DSG1-3 was downregulated in most of the lung cancer cell lines. Reexpression of DSG2 and DSG3 was found in several cancer cell lines after demethylation treatment with 5-aza-2'-deoxycytidine (DAC), a DNA methyltransferase inhibitor. Complete or partial methylation of DSG2 promoter region was detected in 5 out of 6 cancer cell lines by BS. In primary lung tumors, higher protein expression of DSG2 and DSG3 correlated to the diagnosis of squamous cell lung carcinoma (SCC) (P=0.009 and P<0.001, respectively), additionally, a lower expression of DSG3 was significantly linked to higher tumor grade (P=0.012).
  
  
  CONCLUSIONS
  Our data suggest that downregulation of DSG2 and DSG3 could be partially explained by DNA methylation. DSG2 and DSG3 might be potential diagnostic markers for SCC, and DSG3 could be a potential differentiation marker for lung cancer.
authors.affiliation: Institute of Pathology, Jena University Hospital, Ziegelmühlenweg 1, 07740 Jena, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Saaber
authors.affiliation: Institute of Pathology, Jena University Hospital, Ziegelmühlenweg 1, 07740 Jena, Germany.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Pathology, Jena University Hospital, Ziegelmühlenweg 1, 07740 Jena, Germany.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Cui
authors.affiliation: Institute of Pathology, Jena University Hospital, Ziegelmühlenweg 1, 07740 Jena, Germany.
authors.forename: Linlin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Pathology, Jena University Hospital, Ziegelmühlenweg 1, 07740 Jena, Germany.
authors.forename: Masoud
authors.initials: M
authors.lastname: Mireskandari
authors.affiliation: Institute of Pathology, Jena University Hospital, Ziegelmühlenweg 1, 07740 Jena, Germany. Electronic address: iver.petersen@med.uni-jena.de.
authors.forename: Iver
authors.initials: I
authors.lastname: Petersen
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D051183:Desmoglein 1 / Q000378:metabolism*; D051301:Desmoglein 2 / Q000378:metabolism*; D051184:Desmoglein 3 / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D051183:Desmoglein 1; D051301:Desmoglein 2; D051184:Desmoglein 3
keywords: Biomarker; Desmogleins; Methylation; Non-small cell lung cancer