Modulation of the connexin26 tumor suppressor gene expression through methylation in human mammary epithelial cell lines.
BACKGROUND
Normal mammary epithelial cells express mainly gap junction connexin 26 (Cx26) that is either reduced or absent in breast cancers. Since connexin gene mutations are rare we examined if Cx26 gene repression is related to hypermethylation.


METHODS
Five breast epithelial cell lines were examined for Cx26 mRNA expression and hypermethylation. Treatment with a DNA methyltransferase inhibitor, 5-Aza-2'-deoxycytidine (5-Aza-CdR), was carried out to determine if Cx26 gene expression could be upregulated.


RESULTS
Cx26 expression was easily detectable in an immortalized human mammary epithelial cell line (MCF-10) and markedly diminished (MDA-MB231) or undetectable in (MCF-7, BT-20, T47-D) breast cancer cell lines. Hypermethylation of the Cx26 5' region was observed in MCF-10 and MCF-7 cells. Treatment with 5-Aza-CdR resulted in slight or no induction in Cx26 expression in breast cancer cell lines.


CONCLUSIONS
Hypermethylation is unlikely to be a major mechanism for Cx26 gene repression in human mammary cancer cell lines.
Singal
R
R
Department of Medicine, Feist-Weiller Cancer Center, Shreveport, LA, USA. rakeshsingal@hotmail.com
Tu
Z J
ZJ
Vanwert
J M
JM
Ginder
G D
GD
Kiang
D T
DT
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002461:Cell Line, Transformed; D000072259:Connexin 26; D017630:Connexins / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors; D019175:DNA Methylation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D000077209:Decitabine; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D017630:Connexins; D004273:DNA, Neoplasm; C000607042:GJB2 protein, human; D009363:Neoplasm Proteins; D000072259:Connexin 26; D000077209:Decitabine; D004247:DNA; D004248:DNA (Cytosine-5-)-Methyltransferases; D001374:Azacitidine