De novo expression of the Muc2 gene in pancreas carcinoma cells is triggered by promoter demethylation.
It has been established that mucin-producing variants of different subtypes of pancreatic carcinomas, including the intraductal papillary and ductal mucinous tumors, have usually a more favorable prognosis. Intraductal papillary and ductal mucinous tumors have also been shown to ectopically express the intestinal mucin gene MUC2. The mechanism of the de novo expression of this gene in tumors may have potential implications for the modulation of its behavior. We studied, therefore, the mechanism of the de novo expression of MUC2 in pancreas carcinoma cells in vitro. The MUC2 gene promoter is methylated in the nonexpressing pancreatic cell line PANC-1 and is not methylated in the expressing cell line BxPC-3. The promoter is silenced by methylation as shown by reporter expression assays. De novo expression of MUC2 in PANC-1 cells is triggered by treating the cells with a pharmacological inhibitor of DNA methylation (5-aza-2'-deoxycytidine). There was no decrease or loss of expression of the methyltransferase DNMT1 in the MUC2-producing cells. These data show that the de novo expression of the MUC2 gene in pancreas carcinoma cells is associated with promoter demethylation. They warrant further investigations on the relationship between MUC2 promoter demethylation in pancreatic cancer and the prognosis of carcinoma patients.
Siedow
A
A
Medizinische Klinik I, Gastroenterologie und Infektiologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany.
Szyf
M
M
Gratchev
A
A
Kobalz
U
U
Hanski
M-L
ML
Bumke-Vogt
C
C
Foss
H D
HD
Riecken
E O
EO
Hanski
C
C
D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015152:Blotting, Northern; D019175:DNA Methylation; D018076:DNA, Complementary / Q000378:metabolism; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D055262:Mucin-2; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013447:Sulfites / Q000494:pharmacology; D014162:Transfection
D018076:DNA, Complementary; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D012333:RNA, Messenger; D013447:Sulfites; D000077209:Decitabine; D008156:Luciferases; D001374:Azacitidine