Expression of potassium channel isoforms mRNA in normal human adrenals and aldosterone-secreting adenomas.
Increased aldosterone secretion has been found in a mouse lacking the KCNE1 gene which codes for a regulatory protein of the KCNQ1 gene product, forming the channel for the outward rectifying delayed K+ current. Abnormalities in proteins regulating the K+ fluxes across membranes may be responsible for aldosterone-secreting adenomas (aldosteronomas) also because K+ channels are involved in cell growth. Normal and adenomatous adrenal samples and NCI-H295 cell line were used to: a) evaluate KCNE1 and KCNQ1 gene expression, b) sequence the full length cDNAs of KCNE1 and both KCNQ1 isoforms. These differently spliced KCNE1 and KCNQ1 mRNAs were expressed in adrenal tissue. In contrast, KCNQ1 isoform 2 mRNA was not expressed in kidney control tissues and NCl-H295 cell line. NCI-H295 cell line also had a significantly lower expression of KCNQ1 isoform 1 mRNA than normal adrenals and aldosteronomas. We did not find any somatic mutations in the coding sequences of both genes. This different expression pattern of KCNQ1 isoforms in NCI-H295 cell line with the lack of the mRNA for the dominant-negative KCNQ1 isoform 2 supports the involvement of voltage-gated K+ channel in cell proliferation.
Sarzani
R
R
Department of Internal Medicine, Polytechnical University of Marche, Ancona, University of Rome La Sapienza, Rome, Italy. sarzani@univpm.it
Pietrucci
F
F
Francioni
M
M
Salvi
F
F
Letizia
C
C
D'Erasmo
E
E
Dessì Fulgheri
P
P
Rappelli
A
A
D000236:Adenoma / Q000378:metabolism*; D000311:Adrenal Glands / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA
C489622:KCNE1 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024642:Potassium Channels, Voltage-Gated; D000450:Aldosterone