Calcium and epithelial cell proliferation.

The extracellular calcium ion is required for the proliferative activity of a wide variety of nonneoplastic epithelial cells both in vivo and in vitro. This dependence in vitro appears to be density-dependent with sparse cultures unable to proliferate in Ca2+-deficient medium while dense culture can proliferate despite the Ca2+ deficiency. Some epithelial cells have specific cell cycle transitions that require extracellular Ca2+ while most all neoplastic epithelial cells in culture are able to proliferate in Ca2+-deficient media unlike their nonneoplastic controls. The mechanisms of Ca2+ action in nonneoplastic cells involve calmodulin, cyclic AMP and phosphatidylinositol turnover while in neoplastic cells oncogene activation induces the aberrant production of protein products which interact with and deregulate the normal growth-regulatory processes apparently linked to extracellular Ca2+.