Variable promoter region CpG island methylation of the putative tumor suppressor gene Connexin 26 in breast cancer.
Intercellular communication via gap junctions is a mechanism for tumor suppression. Connexin 26 (Cx26) is a structural component of gap junctions expressed by breast epithelial cells. Expression levels of Cx26 are reduced in many breast tumors. Methylation-sensitive single-stranded conformation analysis showed variable methylation in the promoter region CpG island in 11 out of 20 (55%) breast cancer patients. Heterogeneity in methylation patterns was observed both between and within tumors. The degree of methylation ranged from a few CpG dinucleotides to almost all the CpG dinucleotides in the analyzed region. The most frequently methylated CpG was in an Sp1 site known to be important for Cx26 gene expression. One of eight breast cancer cell lines (MD-MBA-453) was methylated in the promoter region and did not express Cx26. Treatment of MDA-MB-453 with 5-aza-2'-deoxycytidine resulted in the re-expression of Cx26 mRNA. Methylation of the promoter region is likely to be an important mechanism in modulating the expression of Cx26 in breast cancer.
Tan
Lor-wai
LW
Department of Haematology-Oncology and University of Adelaide, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia. lorwai.tan@adelaide.edu.au
Bianco
Tina
T
Dobrovic
Alexander
A
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D006801:Humans; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013447:Sulfites / Q000494:pharmacology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D017630:Connexins; C000607042:GJB2 protein, human; D012333:RNA, Messenger; D013447:Sulfites; D000072259:Connexin 26; D000077209:Decitabine; D001374:Azacitidine