title: Decreased expression of RASSF1A and up-regulation of RASSF1C is associated with esophageal squamous cell carcinoma.
abstract: The Ras-Association Domain Family 1 (RASSF1) gene, which is located on the small arm of chromosome 3, contains two CpG islands and generates seven transcripts (RASSF1A-RASSF1G) by differential promoter usage and alternative splicing. As the main transcript, RASSF1A, B and C may play different roles in tumorigenesis. The present study was to detect the role of RASSF1A, B and C in esophageal squamous cell carcinoma (ESCC) and clarify the critical CpG sites of RASSF1A, in order to clarify more information on the role of RASSF1 with regard to the pathogenesis of ESCC. Frequent silencing of RASSF1A but not RASSF1B and RASSF1C were found in esophageal cancer cell lines and the silencing of RASSF1A may be reversed by 5-Aza-dC treatment. The aberrant promoter and exon 1 especially exon 1 methylation of RASSF1A induces silencing of its expression in TE13 cell line. Decreased mRNA and protein expression of RASSF1A was observed in ESCC tumor tissues and was associated with RASSF1A promoter and exon 1 methylation status. Unlike RASSF1A, methylation and expression variation of RASSF1B was not found in ESCC tissues. However, RASSF1C is highly expressed in ESCC tissues. RASSF1A methylation and protein expression were independently associated with ESCC patients' survival. These data indicated that the inactivation of RASSF1A through promoter and exon 1 methylation may play an important role in ESCC carcinogenesis and reactivation of RASSF1A gene may has therapeutic potential and may be used as a prognostic marker for ESCC patients.
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang, 050011, Hebei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
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: Gang
authors.initials: G
authors.lastname: Kuang
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation; D000077209:Decitabine; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C411762:RASSF1 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D001374:Azacitidine
references.citation: Cancer Invest. 2012 Dec;30(10):703-11
references.pmid: 23066640
references.citation: Int J Surg. 2010;8(6):417-22
references.pmid: 20601255
references.citation: Am J Physiol Lung Cell Mol Physiol. 2006 Dec;291(6):L1185-90
references.pmid: 16891396
references.citation: Cancer Res. 2013 Apr 1;73(7):2298-309
references.pmid: 23436800
references.citation: Food Addit Contam. 2007 Feb;24(2):181-5
references.pmid: 17364919
references.citation: Mol Carcinog. 2013 Apr;52(4):265-74
references.pmid: 22213016
references.citation: PLoS One. 2010 Mar 15;5(3):e9668
references.pmid: 20300624
references.citation: BMC Cancer. 2011 Aug 12;11:351
references.pmid: 21838870
references.citation: J Cancer Res Clin Oncol. 2008 Feb;134(2):263-70
references.pmid: 17653764
references.citation: Oncogene. 2002 Jun 20;21(27):4345-9
references.pmid: 12082624
references.citation: Biochim Biophys Acta. 2007 Sep;1776(1):58-85
references.pmid: 17692468
references.citation: Science. 2001 Dec 7;294(5549):2113-5
references.pmid: 11739943
references.citation: World J Gastroenterol. 2007 Dec 14;13(46):6166-71
references.pmid: 18069755
references.citation: Br J Cancer. 2001 Sep 28;85(7):1032-6
references.pmid: 11592776
references.citation: Cancer Lett. 2007 Nov 18;257(2):199-205
references.pmid: 17720308
references.citation: J Biol Chem. 2000 Nov 17;275(46):35669-72
references.pmid: 10998413
references.citation: Bioinformatics. 2002 Nov;18(11):1427-31
references.pmid: 12424112
references.citation: Cancer Res. 2001 Sep 15;61(18):6688-92
references.pmid: 11559536
references.citation: Oncol Rep. 2003 Jul-Aug;10(4):897-901
references.pmid: 12792742
references.citation: Dis Markers. 2007;23(1-2):73-87
references.pmid: 17325427
references.citation: Nat Genet. 2005 Mar;37(3):265-74
references.pmid: 15723065
references.citation: Clin Cancer Res. 2003 Apr;9(4):1441-5
references.pmid: 12684417
references.citation: BMC Cancer. 2010 Oct 18;10:562
references.pmid: 20955597
references.citation: J Natl Cancer Inst. 2001 May 2;93(9):691-9
references.pmid: 11333291
references.citation: Histol Histopathol. 2003 Apr;18(2):665-77
references.pmid: 12647816
references.citation: Cancer Res. 2001 Oct 1;61(19):7034-8
references.pmid: 11585730
references.citation: Arch Med Res. 2011 Apr;42(3):182-8
references.pmid: 21722812
references.citation: Cell. 2007 Feb 23;128(4):683-92
references.pmid: 17320506
references.citation: J Biochem. 1999 Nov;126(5):799-803
references.pmid: 10544270
references.citation: N Engl J Med. 2003 Dec 4;349(23):2241-52
references.pmid: 14657432
references.citation: Cancer Invest. 2009 May;27(4):459-65
references.pmid: 19160099
references.citation: Curr Biol. 2003 Dec 2;13(23):R899-900
references.pmid: 14654011
references.citation: In Silico Biol. 2003;3(3):235-40
references.pmid: 12954087
references.citation: Histol Histopathol. 2005 Apr;20(2):645-63
references.pmid: 15736067
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Nat Genet. 2000 Jul;25(3):315-9
references.pmid: 10888881
references.citation: Mol Cell Biol. 2003 Jan;23(1):206-15
references.pmid: 12482974
references.citation: Oncogene. 2004 Aug 5;23(35):5941-9
references.pmid: 15208682
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7504-9
references.pmid: 11390984
references.citation: N Engl J Med. 2008 Mar 13;358(11):1118-28
references.pmid: 18337602
references.citation: Cancer Res. 2000 Nov 1;60(21):6116-33
references.pmid: 11085536
references.citation: Biochem Biophys Res Commun. 2003 Sep 19;309(2):305-9
references.pmid: 12951050