DNA methylation of K(v)1.3 potassium channel gene promoter is associated with poorly differentiated breast adenocarcinoma.
BACKGROUND
DNA methylation is an important mechanism for gene silencing and has already been described for several genes in breast cancer. A previous immunohistochemistry study demonstrated a decrease of K(v)1.3 potassium channel expression in breast adenocarcinoma compared to normal breast tissue.


METHODS
Methyl-specific PCR (MSP), immunohistochemistry and RNA extraction were performed on breast adenocarcinoma. MSP and DNA extraction were also performed on one breast carcinoma cell line and on primary culture normal cells.


RESULTS
DNA methylation of K(v)1.3 gene promoter was observed in 42.3% of samples (22/52). The methylated status was associated with poorly differentiated tumors (p=0.04) and younger patients (p=0.048). Decreased K(v)1.3 expression was observed in grade III tumors, at both the mRNA and protein levels, while methylation increased in grade III tumors. Finally, K(v)1.3 gene promoter was methylated in the MCF-7 breast carcinoma cell line while promoter methylation was absent in primary culture of normal breast cells (HMEpC).


CONCLUSIONS
We report, for the first time, the methylation of the K(v)1.3 gene promoter in breast adenocarcinoma. Our data suggest that DNA methylation is responsible for a decrease of K(v)1.3 gene expression in breast adenocarcinoma and is associated with poorly differentiated tumors and younger patients.
Brevet
Marie
M
Laboratoire de Physiologie Cellulaire et Moléculaire, Faculté des Sciences, Amiens, France.
Haren
Nathalie
N
Sevestre
Henri
H
Merviel
Philippe
P
Ouadid-Ahidouch
Halima
H
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D051664:Kv1.3 Potassium Channel; D012333:RNA, Messenger