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Ca 2+ channel subunit α 1D promotes proliferation and migration of endometrial cancer cells mediated by 17β‐estradiol via the G protein‐coupled estrogen receptor
Author(s) -
Hao Juan,
Bao Xiaoxia,
Jin Bo,
Wang Xiujuan,
Mao Zebin,
Li Xiaoping,
Wei Lihui,
Shen Danhua,
Wang JianLiu
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-265603
Subject(s) - gper , estrogen , estrogen receptor , medicine , endocrinology , cancer research , endometrial hyperplasia , chemistry , estrogen receptor beta , endometrial cancer , transfection , estrogen receptor alpha , calcium channel , calcium , biology , endometrium , cancer , breast cancer , biochemistry , gene
Calcium and calcium channels are closely related to the estrogen‐induced nongenomic effect of endometrial carcinoma, but the specific role of calcium channels is unknown. This study aimed to explore the expression and the biologic effect of the l ‐type calcium channel in endometrial carcinoma cells and to clarify the molecular mechanism of the relationship between L‐type calcium channels and estrogen. The immunohistochemical results showed that Ca 2+ channel subunit α 1D (Cav1.3) expression was high in atypical hyperplasia (1.90 ± 0.35) and endometrial carcinoma tissues (2.05 ± 0.82) but weak (0.80 ± 0.15) in benign endometrial tissues ( P < 0.05). Treatment with 17b‐estradiol rapidly increased Cav1.3 expression in a dose‐ and time‐dependent manner, and 100 nM cell‐impermeable β‐estradiol‐6‐( O ‐carboxymethyl) oxime:bovine serum albumin also promoted Cav1.3 expression. Transfection with small interfering RNA against G protein‐coupled estrogen receptor (GPER) suppressed estrogen‐induced up‐regulation of Cav1.3 compared with control cells and markedly reduced the estrogen‐induced phosphorylation of ERK1/2 and CREB. Knocking down the Cav1.3 significantly suppressed estrogen‐stimulated Ca 2+ influx, cell proliferation, and migration in endometrial cancer cells. Taken together, Cav1.3 was overexpressed in atypical hyperplasia and endometrial carcinoma, and the estrogen‐induced phosphorylation of downstream molecular ERK1/2 and CREB is the result of activation of the GPER pathway. L‐type channel Cav1.3 is required for estrogen‐stimulated Ca 2+ influx and contributes broadly to the development of endometrial cancer. The Cav1.3 channel may be a new target for endometrial carcinoma treatment.—Hao, J., Bao, X., Jin, B., Wang, X., Mao, Z., Li, X., Wei, L., Shen, D., Wang, J.‐L. Ca + channel subunit a 1D promotes proliferation and migration of endometrial cancer cells mediated by 17β‐estradiol via the G protein‐coupled estrogen receptor FASEB J . 29, 2883‐2893 (2015). www.fasebj.org