DUAL CONTROL OF CELL-GROWTH BY SOMATOMEDINS AND PLATELET-DERIVED GROWTH-FACTOR

Quiescent BALB/c3T3 cells exposed briefly to a platelet-derived growth factor (PDGF) become 'competent' to replicate their DNA but do not 'progress' into S phase unless incubated with growth factors contained in platelet-poor plasma. Plasma from hypophysectomized rats is deficient in progression activity; it does not stimulate PDGF-treated competent cells to synthesize DNA. Addition of somatomedin C to hypophysectomized rat plasma stimulates competent cells to synthesize DNA, demonstrating that somatomedin C is required for progression. Various growth factors were tested for progression activity and competence activity by using BALB/c 3T3 tissue culture assays. Multiplication stimulating activity and other members of the somatomedin family of growth factors are (like somatomedin C) potent mediators of progression. Other mitogenic agents, such as fibroblast growth factor, are (like PDGF) potent inducers of competence. Growth factors with potent progression activity have little or no competence activity and vice versa. In contrast, simian virus 40 provides both competence and progression activity. Coordinate control of BALB/c 3T3 cell growth in vitro by competence factors and somatomedins may be a specific example of a common pattern for growth regulation in animal tissues.