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

Cancer Detect Prev. 2000;24(2):127-36.


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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Alkaline Phosphatase / metabolism
  • Caco-2 Cells / drug effects
  • Caco-2 Cells / metabolism
  • Caco-2 Cells / pathology*
  • Calcium, Dietary / pharmacology*
  • Calcium-Binding Proteins / metabolism*
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Colon / metabolism*
  • Colon / pathology
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Protein Kinase C
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger / analysis
  • Signal Transduction


  • Calcium, Dietary
  • Calcium-Binding Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Protein Kinase C
  • Alkaline Phosphatase