Dietary calcium and growth modulation of human colon cancer cells: role of the extracellular calcium-sensing receptor.

摘要: Using the human colon adenocarcinoma-derived cell line Caco-2, we investigated possible role of Ca2+-sensing receptor (CaR) in mediating effects extracellular Ca2+ on cellular proliferation. Caco-2 cells respond to low ambient [Ca2+]o by activation protein kinase C-signaling pathway, leading upregulation c-myc mRNA expression and thereby, finally, alleviation from G1/S phase control cycle. This proliferative response can be reverted CaR either through raising or, respectively, using agonist Gd3+ as a substitute for Ca2+. The inhibitory effect replication exhibits saturation kinetics (IC50 = 0.045 mM), indicating existence highly sensitive operating at [Ca2+]o. Specific immunostaining revealed presence CaR-positive crypt epithelium normal colonic mucosa well glandular (i.e., differentiated structures) carcinomatous lesions. could provide rationale use calcium supplements intervention early phases tumorigenesis.