Deregulation of 2 potassium channels in pancreas adenocarcinomas: implication of KV1.3 gene promoter methylation.
OBJECTIVE
The aim of this study was to examine expression of 2 potassium (K) channels in pancreatic adenocarcinoma.


METHODS
The immunohistochemical and mRNA expression of GIRK1 (G-protein inwardly rectifying K channel 1) and KV1.3 channel (voltage-dependent K channel) was studied in 55 and 18 adenocarcinomas and 33 and 8 normal pancreas specimens, respectively. The methylation status of KV1.3 promoter was studied by methyl-specific polymerase chain reaction in 33 pancreatic adenocarcinomas. The results were correlated with the patients' prognosis.


RESULTS
GIRK1 was highly expressed in 80% (44/55) of adenocarcinoma samples versus 57.6% (19/33) of normal samples (P=0.03), as confirmed by reverse transcriptase-polymerase chain reaction results (P=0.007). KV1.3 expression was decreased in pancreatic adenocarcinomas compared with normal tissue (7.3% vs 39.4%; P=0.0005). KV1.3 down-expression was associated with metastatic tumors (P=0.018). KV1.3 promoter methylation was observed in 69.7% (22/33) of adenocarcinomas.


CONCLUSIONS
This is the first report of deregulation of 2 K channels in pancreatic adenocarcinoma. GIRK1 was highly expressed in pancreatic adenocarcinomas, corresponding to its role in cell proliferation. Methylation of KV1.3 gene promoter could explain the decrease of KV1.3 expression in adenocarcinomas. New therapeutic agents, such as DNA methylation inhibitors, could be useful against this dramatic cancer.
Brevet
Marie
M
Department of Pathology, CHU Amiens, France.
Fucks
David
D
Chatelain
Denis
D
Regimbeau
Jean-Marc
JM
Delcenserie
Richard
R
Sevestre
Henri
H
Ouadid-Ahidouch
Halima
H
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D016022:Case-Control Studies; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D051664:Kv1.3 Potassium Channel / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D004273:DNA, Neoplasm; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D051664:Kv1.3 Potassium Channel; D012333:RNA, Messenger