title: Downregulation of CD44v6 in colorectal carcinomas is associated with hypermethylation of the CD44 promoter region.
abstract: Overexpression of the cell adhesion protein CD44v6 has been demonstrated in colorectal cancer and other gastrointestinal tumors. While CD44v6 is upregulated in benign colorectal adenomas and well-differentiated colorectal cancer tissues, downregulation frequently occurs during disease progression. The mechanism of downregulation, however, is unknown. Therefore, we evaluated the methylation status of the CD44 promoter as a mechanism for decreased CD44v6 expression in advanced colorectal carcinomas. We demonstrated by methylation-sensitive restriction enzyme digestion that the CpG islands of the CD44 promoter were methylated in 6/21 (28%) of benign colorectal adenomas. Interestingly, in colorectal carcinomas the frequency of promoter methylation was significantly increased (10/19; 53%) compared to 7/21 (33%) in the corresponding normal mucosa. Methylation seems to be associated with a more advanced cancer stage, but the trend did not reach statistical significance. In colorectal carcinomas with CD44 promoter methylation CD44v6 mRNA was detected by reverse transcription-polymerase chain reaction in 3/10 carcinomas, whereas in tumors without CD44 promoter methylation CD44v6 expression was observed in 8/9 (P <or= 0.05). These results demonstrated that methylation of the 5'CpG island of the CD44 gene is closely associated with decreased expression of CD44v6 in human colorectal carcinomas.
authors.affiliation: Department of Internal Medicine II, Saarland University, Homburg/Saar, Germany. inasta@uniklinik-saarland.de
authors.forename: A
authors.initials: A
authors.lastname: Stallmach
authors.forename: B M
authors.initials: BM
authors.lastname: Wittig
authors.forename: K
authors.initials: K
authors.lastname: Kremp
authors.forename: R
authors.initials: R
authors.lastname: Goebel
authors.forename: S
authors.initials: S
authors.lastname: Santourlidis
authors.forename: M
authors.initials: M
authors.lastname: Zeitz
authors.forename: M
authors.initials: M
authors.lastname: Menges
authors.forename: J
authors.initials: J
authors.lastname: Raedle
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
authors.forename: W A
authors.initials: WA
authors.lastname: Schulz
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018899:CpG Islands; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D008745:Methylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C112697:CD44v6 antigen; D017931:DNA Primers; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D012333:RNA, Messenger