Friederike Saaber1, Yuan Chen1, Tiantian Cui1, Linlin Yang1, Masoud Mireskandari1, Iver Petersen2. 1. Institute of Pathology, Jena University Hospital, Ziegelmühlenweg 1, 07740 Jena, Germany. 2. Institute of Pathology, Jena University Hospital, Ziegelmühlenweg 1, 07740 Jena, Germany. Electronic address: iver.petersen@med.uni-jena.de.
Abstract
AIMS: 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.
AIMS: 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 humanlung 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: Daniel T Merrick; Michael G Edwards; Wilbur A Franklin; Michio Sugita; Robert L Keith; York E Miller; Micah B Friedman; Lori D Dwyer-Nield; Meredith A Tennis; Mary C O'Keefe; Elizabeth J Donald; Jessica M Malloy; Adrie van Bokhoven; Storey Wilson; Peter J Koch; Charlene O'Shea; Christopher Coldren; David J Orlicky; Xian Lu; Anna E Baron; Greg Hickey; Timothy C Kennedy; Roger Powell; Lynn Heasley; Paul A Bunn; Mark Geraci; Raphael A Nemenoff Journal: Cancer Res Date: 2018-07-11 Impact factor: 12.701
Authors: Allison S Cohen; Farah K Khalil; Eric A Welsh; Matthew B Schabath; Steven A Enkemann; Andrea Davis; Jun-Min Zhou; David C Boulware; Jongphil Kim; Eric B Haura; David L Morse Journal: Oncotarget Date: 2017-12-07