Growth Factors and Regulation of Cell Growth

Abstract

A new class of polypeptide hormones known collectively as growth factors has been identified. These polypeptides are able to stimulate DNA synthesis and mitosis of cells cultured in vitro. Growth factors have been isolated from several sources, including platelets, submaxillary glands, pituitary, brain, and medium conditioned by cells grown in vitro. Growth factors appear to behave like classic polypeptide hormones. In the cases of epidermal growth factor and nerve growth factor, specific cell membrane receptors have been studied in detail and partially purified. Platelet-derived growth factor and somatomedin-C interact synergistically and apparently, sequentially to promote cell proliferation in vitro. These studies suggest that cell proliferation is controlled by a synergistic interaction among several growth factors and, perhaps, other hormones. Several in vivo roles for growth factors and a role for tumor-cell-derived growth factors in neoplasia have been suggested.

Transduction of Growth or Mitogenic Signals into Translational Activation of TOP mRNAs Is Fully Reliant on the Phosphatidylinositol 3-Kinase-Mediated Pathway but Requires neither S6K1 nor rpS6 Phosphorylation

“…When cells are stimulated by growth factors, they display a wide variety of responses, including increased protein synthesis (2). A well-documented pathway which transduces mitogenic or growth signals involves PI3-kinase and its downstream effector, PKB (32).…”

Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha 1 adrenergic response.

“…Myocardial glucose transport (16) and phosphofructokinase activity (17) may be under alpha adrenergic control. Activation of glucose transport and phosphofructokinase are early events when growth factors stimulate cell hyperplasia (18). Since cells enlarge before division, these same events may be important when cells grow by hypertrophy.…”

Human platelet-derived growth factor stimulates prostaglandin synthesis by activation and by rapid de novo synthesis of cyclooxygenase.

“…We have used quiescent Swiss 3T3 cells stimulated to divide by platelet-derived growth factor (PDGF), the principal mitogen for connective tissue-derived cells (1 [1][2][3][4][5][6][7][8][9][10][11][12][13], as model systems to study the relation between growth factor-induced changes in phospholipid metabolism and AA release (14-16). Cells maintained in plasma-derived serum (PDS) become arrested in the GO/GI phase of the cell cycle and can be stimulated to undergo cell cycle traverse after stimulation by PDGF in a partially synchronized fashion (17).…”