Calcitriol stimulates gene expression of cathelicidin antimicrobial peptide in breast cancer cells with different phenotype.

ABSTRACT: BACKGROUND:In normal and neoplastic cells, growth-promoting, proangiogenic, cytotoxic and pro-apoptotic effects have all been attributed to cathelicidin antimicrobial peptide (CAMP). Nevertheless, little is known about the factors regulating this peptide expression in breast cancer. Herein we asked if the well-known antineoplastic hormone calcitriol could differentially modulate CAMP gene expression in human breast cancer cells depending on the cell phenotype in terms of efficacy and potency. METHODS:The established breast cancer cell lines MCF7, BT-474, HCC1806, HCC1937, SUM-229PE and a primary cell culture generated from invasive ductal breast carcinoma were used in this study. Calcitriol regulation of cathelicidin gene expression in vitro and in human breast cancer xenografts was studied by real time PCR. Tumorigenicity was evaluated for each cell line in athymic mice. RESULTS:Estrogen receptor (ER)??+?breast cancer cells showed the highest basal CAMP gene expression. When incubated with calcitriol, CAMP gene expression was stimulated in a dose-dependent and cell phenotype-independent manner. Efficacy of calcitriol was lower in ER??+?cells when compared to ER?- cells (<10 vs. >70 folds over control, respectively). Conversely, calcitriol lowest potency upon CAMP gene expression was observed in the ER?-/EGFR+ SUM-229PE cell line (EC50?=?70.8 nM), while the highest was in the basal-type/triple-negative cells HCC1806 (EC50?=?2.13 nM) followed by ER??+?cells MCF7 and BT-474 (EC50?=?4.42 nM and 14.6 nM, respectively). In vivo, lower basal CAMP gene expression was related to increased tumorigenicity and lack of ER? expression. Xenografted triple-negative breast tumors of calcitriol-treated mice showed increased CAMP gene expression compared to vehicle-treated animals. CONCLUSIONS:Independently of the cell phenotype, calcitriol provoked a concentration-dependent stimulation on CAMP gene expression, showing greater potency in the triple negative HCC1806 cell line. Efficacy of calcitriol was lower in ER??+?cells when compared to ER?- cells in terms of stimulating CAMP gene expression. Lower basal CAMP and lack of ER? gene expression was related to increased tumorigenicity. Our results suggest that calcitriol anti-cancer therapy is more likely to induce higher levels of CAMP in ER?- breast cancer cells, when compared to ER??+?breast cancer cells.

SUBMITTER: Garcia-Quiroz J 

PROVIDER: S-EPMC5103596 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature