title: Calcium regulation of growth and differentiation of mouse epidermal cells in culture.
abstract: Modification of the ionic calcium concentration in the culture medium markedly alters the pattern of proliferation and differentiation in cultured mouse epidermal cells. When medium calcium is lowered to 0.05--0.1 mM, keratinocytes proliferate rapidly with a high growth fraction and do not stratify, but continue to synthesize keratin. The cells grow as a monolayer for several months and can be subcultured and cloned in low Ca++ medium. Ultrastructural examination of cells cultured under low Ca++ conditions reveals widened intercellular spaces, abundant microvilli and perinuclear organization of tonofilaments and cellular organelles. Desmosomes are absent. Epidermal cells growing as a monolayer in low Ca++ can be induced to terminally differentiate by adding calcium to the level normally found in the culture medium (1.2 mM). Cell-to-cell contact occurs rapidly and desmosomes form within 2 hr. The cells stratify by 1--2 days and terminally differentiate with cell sloughing by 3--4 days. After Ca++ addition, DNA synthesis decreases with a lag of 5--10 hr and is totally inhibited within 34 hr. In contrast, RNA and protein synthesis continue at 40--50% of the low Ca++ level at day 3, a time when many cells are detaching from the culture dish. Keratin synthesis is unaffected by the Ca++ switch.
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D003896:Desmosomes / Q000187:drug effects; D000078404:Epidermal Cells; D007633:Keratins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008871:Microvilli / Q000648:ultrastructure; D009940:Organoids / Q000648:ultrastructure; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis
chemical_list: D012313:RNA; D007633:Keratins; D004247:DNA; D002118:Calcium