title: RASSF5A, a candidate tumor suppressor, is epigenetically inactivated in esophageal squamous cell carcinoma.
abstract: As a result of alternative splicing and differential promoter usage, RASSF5 exists in at least three isoforms (RASSF5A-RASSF5C), which may play different roles in tumorigenesis. The present study was to detect the role of RASSF5A, B and C in esophageal squamous cell carcinoma (ESCC) and clarify the critical CpG sites of RASSF5A, in order to clarify more information on the role of RASSF5 with regard to the pathogenesis of ESCC. Frequent silencing of RASSF5A but not RASSF5B and RASSF5C were found in esophageal cancer cell lines and the silencing of RASSF5A may be reversed by 5-Aza-dC or TSA treatment. The aberrant CpG island 1 methylation of RASSF5A induces silencing of its expression in TE13 cell line. Decreased mRNA and protein expression of RASSF5A was observed in ESCC tumor tissues and was associated with RASSF5A CpG island 1 methylation status. Unlike RASSF5A, expression variation of RASSF5B and RASSF5C was not found in ESCC tissues. Aberrant promoter methylation of RASSF5C was also not found in ESCC. RASSF5A methylation and protein expression were independently associated with ESCC patients' survival. These data indicated that the inactivation of RASSF5A through CpG island 1 methylation may play an important role in ESCC carcinogenesis, RASSF5A may be a functional tumor suppressor and may serve as a prognostic biomarker for ESCC.
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang, Hebei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Guo
authors.forename: Supeng
authors.initials: S
authors.lastname: Shen
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Gang
authors.initials: G
authors.lastname: Kuang
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Dong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D017398:Alternative Splicing / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D003570:Cytidine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004947:Esophagus / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D023121:RNA, Messenger, Stored / Q000096:biosynthesis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D006877:Hydroxamic Acids; D020033:Protein Isoforms; D011500:Protein Synthesis Inhibitors; C454042:RASSF5 protein, human; D023121:RNA, Messenger, Stored; C012589:trichostatin A; D003570:Cytidine Triphosphate; C038673:5-aza-2'-deoxycytidine-5'-triphosphate; D020559:Monomeric GTP-Binding Proteins; D001374:Azacitidine