Upregulation of ATP-sensitive potassium channels for estrogen-mediated cell proliferation in human uterine leiomyoma cells.
OBJECTIVE
The objectives of the present study were to evaluate the expression level of ATP-sensitive potassium (K(ATP)) channels in smooth muscle cells in human uterine leiomyoma and the involvement of the channel in potentiating effect of estrogen on leiomyoma growth.


METHODS
Reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR and Western blot were used for the identification and quantification of K(ATP)-channel subunits in the control myometrial and leiomyoma cells. Furthermore, we measured the K(ATP)-channel activity in enzymatically isolated single uterine smooth muscle cells by whole-cell patch-clamp recordings. The estrogen-induced cell proliferation in leiomyoma was measured by the MTT assay.


RESULTS
The subunits of K(ATP) channels (Kir6.1, Kir6.2, SUR2B) were more highly expressed in leiomyoma cells than in control cells. The whole-cell currents mainly through K(ATP) channels were also greater in the leiomyoma cells. Estrogen applied in the bath solution could acutely enhance the channel activity. Estrogen-induced proliferation of the leiomyoma cells was inhibited by pretreatment with glibenclamide, a K(ATP)-channel inhibitor.


CONCLUSIONS
Estrogen may induce the proliferation of leiomyoma cells, at least in part, by activating the K(ATP) channel. Increased expression of the K(ATP) channel may be a causal factor for the high growth rate of uterine leiomyoma.
Park
Sung-Hee
SH
Department of Physiology, Keimyung University School of Medicine, Daegu, South Korea.
Ramachandran
Sabarish
S
Kwon
Sang-Hoon
SH
Cha
Soon-Do
SD
Seo
Eul Won
EW
Bae
Insoo
I
Cho
Chiheum
C
Song
Dae-Kyu
DK
D000328:Adult; D048708:Cell Growth Processes / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics; D047629:Estrogen Receptor beta / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005562:Formazans / Q000737:chemistry; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D054086:KATP Channels / Q000096:biosynthesis* / Q000235:genetics; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D020110:Pinacidil / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000737:chemistry; D015854:Up-Regulation / Q000187:drug effects; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005562:Formazans; D054086:KATP Channels; D012333:RNA, Messenger; D013778:Tetrazolium Salts; C079782:MTT formazan; D004958:Estradiol; D020110:Pinacidil; D005905:Glyburide