title: Correlation between T-cadherin gene expression and aberrant methylation of T-cadherin promoter in human colon carcinoma cells.
abstract: Previous researches showed T-cadherin (CDH13) expression was downregulated in colon cancer tissues and was associated with increase of invasive and metastatic potential. This research was to observe the mechanisms responsible for inactivation of T-cadherin gene in colon carcinoma; we investigated the methylation status around the 5' promoter region of T-cadherin gene of Hct116 colon cancer cell line by methylation-specific polymerase chain reaction (MSP), also detected the expression change of T-cadherin mRNA and protein in Hct116 cell line after 5-Aza-CdR treatment by reverse transcriptase polymerase chain reaction and Western blotting, and compared the T-cadherin methylation status with T-cadherin mRNA and protein expression. We found that hypermethylation of T-cadherin was involved in Hct116 cell line, while T-cadherin mRNA and protein expression was almost lost or downregulated in Hct116 cell line. Therefore, methylation of the T-cadherin promoter region was correlated with the loss or downregulation of T-cadherin mRNA and protein expression in Hct116 colon cancer cell line. Treatment of T-cadherin-negative carcinoma cells with the demethylating agent, 5-aza-2'-deoxycytidine, induced re-expression of this gene. Our findings demonstrate that 5' CpG island methylation is common in colon carcinoma and may play an important role in the inaction of T-cadherin. Our results also suggest that demethylation of the T-cadherin gene may be a potential therapeutic strategy for colon carcinoma.
authors.affiliation: Department of Gastroenterology, Xiangya 2nd Hospital, Central South University, Changsha, China.
authors.forename: Jian-Zhen
authors.initials: JZ
authors.lastname: Ren
authors.forename: Ji-Rong
authors.initials: JR
authors.lastname: Huo
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; C099972:H-cadherin; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine