Calcitriol stimulates gene expression of cathelicidin antimicrobial peptide in breast cancer cells with different phenotype. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: García-Quiroz, Janice; García-Becerra, Rocío; Santos-Martínez, Nancy; Avila, Euclides; Larrea, Fernando; Díaz, Lorenza
• Is Part Of: Journal of biomedical science. Volume 23:Issue 1(2016)
• Page Start: 1
• Page End: 7
• Publication Date: 2016-12
• Subjects: Cathelicidin -- Breast cancer -- LL-37 -- Calcitriol -- Vitamin D; Medical sciences -- Periodicals; 610.28
• DOI: 10.1186/s12929-016-0298-4
• Languages: English
• ISSNs: 1021-7770

Abstract

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 modulateCAMP 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)α + breast cancer cells showed the highest basalCAMP 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 ERα + cells when compared to ERα- cells (<10 vs. >70 folds over control, respectively). Conversely, calcitriol lowest potency uponCAMP gene expression was observed in the ERα-/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 ERα + cells MCF7 and BT-474 (EC50 = 4.42 nM and 14.6 nM, respectively). In vivo, lower basalCAMP gene expression was related to increased tumorigenicity and lack of ERα expression. Xenografted triple-negative breast tumors of calcitriol-treated mice showed increasedCAMP gene expression compared to vehicle-treated animals. Conclusions Independently of the cell phenotype, calcitriol provoked a concentration-dependent stimulation onCAMP gene expression, showing greater potency in the triple negative HCC1806 cell line. Efficacy of calcitriol was lower in ERα + cells when compared to ERα- cells in terms of stimulatingCAMP gene expression. Lower basalCAMP and lack of ERα gene expression was related to increased tumorigenicity. Our results suggest that calcitriol anti-cancer therapy is more likely to induce higher levels ofCAMP in ERα- breast cancer cells, when compared to ERα + breast cancer cells.