Calcitriol inhibits Ether-à go-go potassium channel expression and cell proliferation in human breast cancer cells.
Antiproliferative actions of calcitriol have been shown to occur in many cell types; however, little is known regarding the molecular basis of this process in breast carcinoma. Ether-à-go-go (Eag1) potassium channels promote oncogenesis and are implicated in breast cancer cell proliferation. Since calcitriol displays antineoplastic effects while Eag1 promotes tumorigenesis, and both factors antagonically regulate cell cycle progression, we investigated a possible regulatory effect of calcitriol upon Eag1 as a mean to uncover new molecular events involved in the antiproliferative activity of this hormone in human breast tumor-derived cells. RT real-time PCR and immunocytochemistry showed that calcitriol suppressed Eag1 expression by a vitamin D receptor (VDR)-dependent mechanism. This effect was accompanied by inhibition of cell proliferation, which was potentiated by astemizole, a nonspecific Eag1 inhibitor. Immunohistochemistry and Western blot demonstrated that Eag1 and VDR abundance was higher in invasive-ductal carcinoma than in fibroadenoma, and immunoreactivity of both proteins was located in ductal epithelial cells. Our results provide evidence of a novel mechanism involved in the antiproliferative effects of calcitriol and highlight VDR as a cancer therapeutic target for breast cancer treatment and prevention.
García-Becerra
Rocío
R
Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No 15, Tlalpan 14000 México, DF, Mexico.
Díaz
Lorenza
L
Camacho
Javier
J
Barrera
David
D
Ordaz-Rosado
David
D
Morales
Angélica
A
Ortiz
Cindy Sharon
CS
Avila
Euclides
E
Bargallo
Enrique
E
Arrecillas
Myrna
M
Halhali
Ali
A
Larrea
Fernando
F
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002117:Calcitriol / Q000494:pharmacology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018167:Receptors, Calcitriol / Q000378:metabolism
D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D018167:Receptors, Calcitriol; D002117:Calcitriol