title: Ca2+ channel subunit α 1D promotes proliferation and migration of endometrial cancer cells mediated by 17β-estradiol via the G protein-coupled estrogen receptor.
abstract: 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 17β-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.
authors: *Department of Obstetrics and Gynaecology and Department of Pathology, Peking University People's Hospital, Beijing, China; and Department of Biochemistry and Molecular Biology, Peking University, Beijing, China.
authors: Juan
authors: J
authors: Hao
authors: *Department of Obstetrics and Gynaecology and Department of Pathology, Peking University People's Hospital, Beijing, China; and Department of Biochemistry and Molecular Biology, Peking University, Beijing, China.
authors: Xiaoxia
authors: X
authors: Bao
authors: *Department of Obstetrics and Gynaecology and Department of Pathology, Peking University People's Hospital, Beijing, China; and Department of Biochemistry and Molecular Biology, Peking University, Beijing, China.
authors: Bo
authors: B
authors: Jin
authors: *Department of Obstetrics and Gynaecology and Department of Pathology, Peking University People's Hospital, Beijing, China; and Department of Biochemistry and Molecular Biology, Peking University, Beijing, China.
authors: Xiujuan
authors: X
authors: Wang
authors: *Department of Obstetrics and Gynaecology and Department of Pathology, Peking University People's Hospital, Beijing, China; and Department of Biochemistry and Molecular Biology, Peking University, Beijing, China.
authors: Zebin
authors: Z
authors: Mao
authors: *Department of Obstetrics and Gynaecology and Department of Pathology, Peking University People's Hospital, Beijing, China; and Department of Biochemistry and Molecular Biology, Peking University, Beijing, China.
authors: Xiaoping
authors: X
authors: Li
authors: *Department of Obstetrics and Gynaecology and Department of Pathology, Peking University People's Hospital, Beijing, China; and Department of Biochemistry and Molecular Biology, Peking University, Beijing, China.
authors: Lihui
authors: L
authors: Wei
authors: *Department of Obstetrics and Gynaecology and Department of Pathology, Peking University People's Hospital, Beijing, China; and Department of Biochemistry and Molecular Biology, Peking University, Beijing, China.
authors: Danhua
authors: D
authors: Shen
authors: *Department of Obstetrics and Gynaecology and Department of Pathology, Peking University People's Hospital, Beijing, China; and Department of Biochemistry and Molecular Biology, Peking University, Beijing, China wangjianliu@pkuph.edu.cn.
authors: Jian-Liu
authors: JL
authors: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D002417:Cattle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004714:Endometrial Hyperplasia / Q000235:genetics / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D020935:MAP Kinase Signaling System; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C472073:CACNA1D protein, human; C115163:CREB1 protein, human; D020746:Calcium Channels, L-Type; D017362:Cyclic AMP Response Element-Binding Protein; C109584:GPER1 protein, human; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D004958:Estradiol
keywords: Cav1.3; ERK1/2; calcium; endometrial carcinoma; rapid signaling effect