[Intermediate-conductance-Ca2+-activated K+ channels are overexpressed in endometrial cancer and involved in regulating proliferation of endometrial cancer cells].
OBJECTIVE
To study the expression of intermediate-conductance-Ca(2+)-activated K(+) (IKCa1) channels in endometrial cancer and its role in regulating proliferation of endometrial cancer cells.


METHODS
Western blot and RT-PCR were used to examine the expression of IKCa1 channels in 13 normal endometrial specimens and 25 endometrial cancer specimens; and RNA interference (RNAi), [(3)H] thymidine incorporation, and inhibitor of IKCa1 channel were used to explore the role of IKCa1 channels in regulation of proliferation of endometrial cancer cells HEC-1A.


RESULTS
The expression rate and level of IKCa1 mRNA in endometrial carcinoma (84%, 0.89 +/- 0.52) were higher than in normal endometria (8%, 0.14 +/- 0.12; P < 0.01). The expression rate and level of IKCa1 protein in endometrial carcinomas (80%, 1.18 +/- 0.41) were higher than in normal endometria (15%, 0.71 +/- 0.26; P < 0.01). Clotrimazole, an inhibitor of IKCa1 channels known to suppress the function of the channels, caused a both time- and dose-dependent decrease in cell number of HEC-1A cell. Western blot analysis revealed that the IKCa1 level in whole lysates of the cells transfected with target-IKCa1 small interference RNA (siRNA) was (48.27 +/- 9.07)% of that found in the cells transfected with non-silencing RNA; [(3)H] thymidine incorporation in HEC-1A cells transfected with target-IKCa1 siRNA was also reduced, siRNA inhibited HEC-1A cell proliferation, compared with the cells transfected with non-silencing RNA (P < 0.05).


CONCLUSIONS
The expression of IKCa1 channels may be closely related to the proliferation of endometrial cancer, and down regulation of its expression may suppress its development.
Wang
Zhen-Hua
ZH
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
Feng
You-Ji
YJ
Su
Min
M
Yi
Xiao-Fang
XF
D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003022:Clotrimazole / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D003022:Clotrimazole