title: Membrane stabilization by intimate contact between cells reduces their Mg2+ activity and suppresses the neoplastic phenotype.
abstract: The mechanism of normalizing transformed cells by contact with normal cells is considered in relation to the mechanism of stimulating the growth of normal contact-inhibited cells. Stimulation is based on perturbation of the plasma membrane throughout the G1 period by growth factors. A primary effect of the membrane perturbation is a long-sustained increase of intracellular free Mg(2+) which increases the initiation frequency of polypeptide synthesis and accelerates the onset of DNA synthesis. Because the plasma membrane of transformed cells is kept in a continuously perturbed state and forms poor intercellular adhesions, it loses control of intracellular Mg(2+) activity. However, maximizing contact between transformed cells at extremely high density stabilizes their plasma membrane, lowers their Mg(2+) content and normalizes their phenotype. Normalization may also be obtained in contact with lower densities of quiescent, confluent normal cells. Evidence against a need for junctional communication supports membrane stabilization with restoration of Mg(2+) regulation as the mechanism of normalization.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA. hrubin@uclinik4.berkeley.edu
authors.forename: Harry
authors.initials: H
authors.lastname: Rubin
mesh_terms: D000818:Animals; D002413:Cations, Divalent / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology; D008274:Magnesium / Q000378:metabolism*; D010641:Phenotype; D014176:Protein Biosynthesis / Q000502:physiology
chemical_list: D002413:Cations, Divalent; D008274:Magnesium