Description and role in proliferation of iberiotoxin-sensitive currents in different human mammary epithelial normal and cancerous cells.
Several studies suggested that potassium channels are involved in the proliferation of cancer cells but the involvement of the large conductance Ca2+-activated K+ channels (BKCa) in the cancerous phenomenon is still controversial. In the present study, we used iberiotoxin, a specific blocker of BKCa, and report the activity of an iberiotoxin-sensitive current in various human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-468 and MDA-MB-435s) as well as in normal mammary epithelial cells (HME). Iberiotoxin and NS1619, an activator of BKCa, did not interfere with either cell proliferation or with the invasive properties of the cells, under normal culture conditions. However, extracellular pulses of ATP, which induced transient increases in intracellular Ca2+ concentration, revealed a significant reduction effect of iberiotoxin on cell proliferation. We conclude that the iberiotoxin-sensitive current is not involved in cell proliferation in basal conditions but participates when the intracellular Ca2+ concentration is increased. These experiments also suggest that BKCa channels are not involved in the cancerous transformation and are probably a relic from normal cells.
Roger
Sébastien
S
Nutrition, Croissance et Cancer. Equipe mixte INSERM-Université Emi-U 0211, Faculté de Médecine, 8 bis Bd Tonnellé, 37032 Tours Cedex, France.
Potier
Marie
M
Vandier
Christophe
C
Le Guennec
Jean-Yves
JY
Besson
Pierre
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology; D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004553:Electric Conductivity; D004848:Epithelium / Q000187:drug effects*; D005260:Female; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects
D001562:Benzimidazoles; D005456:Fluorescent Dyes; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C086491:NS 1619; C064719:iberiotoxin; D000255:Adenosine Triphosphate; D002118:Calcium; D016257:Fura-2