title: Calcitriol inhibits Ether-à go-go potassium channel expression and cell proliferation in human breast cancer cells.
abstract: 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.
authors.affiliation: Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No 15, Tlalpan 14000 México, DF, Mexico.
authors.forename: Rocío
authors.initials: R
authors.lastname: García-Becerra
authors.forename: Lorenza
authors.initials: L
authors.lastname: Díaz
authors.forename: Javier
authors.initials: J
authors.lastname: Camacho
authors.forename: David
authors.initials: D
authors.lastname: Barrera
authors.forename: David
authors.initials: D
authors.lastname: Ordaz-Rosado
authors.forename: Angélica
authors.initials: A
authors.lastname: Morales
authors.forename: Cindy Sharon
authors.initials: CS
authors.lastname: Ortiz
authors.forename: Euclides
authors.initials: E
authors.lastname: Avila
authors.forename: Enrique
authors.initials: E
authors.lastname: Bargallo
authors.forename: Myrna
authors.initials: M
authors.lastname: Arrecillas
authors.forename: Ali
authors.initials: A
authors.lastname: Halhali
authors.forename: Fernando
authors.initials: F
authors.lastname: Larrea
mesh_terms: 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
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D018167:Receptors, Calcitriol; D002117:Calcitriol