Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
ROLE OF PDGF-LIKE GROWTH FACTORS IN AUTOCRINE STIMULATION OF GROWTH OF NORMAL AND TRANSFORMED CELLS
Oncogenes and Growth Control. Kahn P et al, eds. New York, Springer-Verlag, p. 43-50, 1986.. Unique Identifier : AIDSLINE ICDB/87637966 Heldin CH; Westermark B; Uppsala Branch of the Ludwig Cancer Institute for Cancer; Research, Biomedical Center, S-751 23 Uppsala, Sweden
Abstract:
Platelet-derived growth factor (PDGF) and related factors, together with their possible roles in autocrine and paracrine mechanisms in both normal and transformed cells, are reviewed. PDGF is composed of two disulfide-bonded polypeptide chains, denoted A and B. The amino acid sequence of the PDGF B chain is almost identical to that of a portion of p28(v-sis), the transforming protein of simian sarcoma virus (SSV). The primary translation product of v-sis, p28(v-sis), is rapidly dimerized after synthesis; the apparently stable end product of mol wt 24,000 is structurally similar to a PDGF B chain homodimer. Cell lines derived from tumors produce growth factors that bind to PDGF receptor; one of these lines is U2 OS, a human osteosarcoma that secretes a growth factor with structural, immunological, and functional properties in common with PDGF. Analysis of this osteosarcoma-derived growth factor showed that it is a homodimer of PDGF A chain. Using mRNA from a clone of the human glioma cell line U343 MGa Cl 2, which also produces a PDGF-like growth factor, cDNA for the A chain of PDGF was cloned and sequenced. The A and B chains of PDGF showed extensive homology. Autocrine and paracrine mechanisms may operate not only in cell transformation but in the stimulation of normal, controlled cell growth under certain conditions. For example, cytotrophoblasts of early human placenta express a c-sis transcript; this expression correlates with expression of c-myc. Furthermore, cultured cytotrophoblasts secrete a PDGF-like growth factor, have PDGF receptors, and respond to PDGF stimulation by showing increased c-myc expression. These observations suggest that PDGF may stimulate placental growth during a defined phase of embryogenesis. The phenotypic characteristics of SSV-transformed cells agree with a simple model of SSV-transformation that postulates an autocrine stimulation brought about by a growth factor mimicking PDGF in its functions but having no additional activity. (34 Refs)
Keywords: Animal *Cell Division Cell Line *Cell Transformation, Neoplastic Cell Transformation, Viral Gene Expression Regulation Human Neoplasms Platelet-Derived Growth Factor/*PHYSIOLOGY Receptors, Cell Surface/*PHYSIOLOGY Sarcoma Viruses, Simian/GENETICS MONOGRAPH
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Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
