Upregulation of ATP-sensitive potassium channels for estrogen-mediated cell proliferation in human uterine leiomyoma cells

Abstract

Objectives. The objectives of the present study were to evaluate the expression level of ATP-sensitive potassium (KATP) 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 KATP-channel subunits in the control myometrial and leiomyoma cells. Furthermore, we measured the KATP-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 KATP channels (Kir6.1, Kir6.2, SUR2B) were more highly expressed in leiomyoma cells than in control cells. The whole-cell currents mainly through KATP 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 KATP-channel inhibitor. Conclusion. Estrogen may induce the proliferation of leiomyoma cells, at least in part, by activating the KATP channel. Increased expression of the KATP channel may be a causal factor for the high growth rate of uterine leiomyoma. Keywords: Uterine leiomyoma, KATP channel, estrogen, cell proliferation Introduction Uterine leiomyoma (fibroids/myomas) is a common problem, occurring in 40% of women older than 35 years. The availability of a safe and effective nonsurgical treatment of leiomyoma would be of considerable clinical and public health importance. Uterine leiomyoma is a monoclonal tumor, and the factors involved in its initiation and growth remain poorly understood. Reports state that ovarian steroids, i.e. progesterone and estrogen [1,2], participate in the