Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
GROWTH FACTORS AND RECEPTORS
Molecular Genetics in Cancer Diagnosis. Cossman J, ed. New York, Elsevier, p. 49-72, 1990.. Unique Identifier : AIDSLINE ICDB/91676245 Leonard WJ; Sharon M; Natl. Inst. of Child Health and Human Development, Bethesda, MD
Abstract:
In contrast to the carefully regulated growth control of normal diploid cells, transformed or malignant cells can grow in the absence of exogenous growth factors. The identification of oncogenes and the recognition that some of these oncogenes encode protein with significant homology to cellular growth factor receptors have encouraged the view that the mechanisms of oncogenesis can be discovered. Data related to a variety of growth factor/growth factor receptor systems are summarized here, and the interleukin-2 (IL-2)/IL-2 receptor system is described in detail. Topics include platelet-derived growth factor (PDGF); epidermal growth factor (EGF); nerve growth factor (NGF) and NGF receptors; transforming growth factor beta (TGF-b); insulin-like growth factors; IL-1 and IL-1 receptors; hematopoietic colony-stimulating factors; IL-4 and IL-4 receptors; IL-6; tumor necrosis factor; tyrosine kinases; and IL-2 and immune response (IL-2 receptors, p55 [Tac antigen], structure of high-, intermediate-, and low-affinity IL-2 receptor model for leukemogenesis in adult T-cell leukemia, and IL-2 receptors in diagnosis and management of the pathologic state). Growth factors and growth factor receptors can relate to malignancies in various ways. In some examples, such as the PDGF, IL-2, and IL-6 systems, it appears that the malignant phenotype can be correlated with autocrine growth mediated through inappropriate expression of growth factor and its receptor. Appropriate mutations of the receptor or overexpression of the EGF receptor can result in EGF-independent or EGF-dependent phenotypes. However, neither mere overexpression of cell surface receptors (as occurs with IL-2 receptors) nor providing exogenous ligand (as occurs with PDGF) are necessarily sufficient for transformation. In the TGF-b system, rather than directly resulting in autocrine cell growth, TGF-b appears to mediate potential tumorigenic effects by affecting the cell stroma and/or by compromising the quality of the normal immune surveillance. Also, growth factor/growth factor receptor interactions actually can lead to decreased growth in specialized circumstances involving cell lines, as in both the IL-2 and EGF systems. IL-2 receptor expression can be deregulated in adult T-cell leukemia, where an autocrine or paracrine mechanism of leukemogenesis is postulated. The number of ways in which growth factor/growth factor receptors potentially can relate to oncogenesis and treatment of cancer obviously are numerous, making these critical for further basic and clinical investigation. (146 Refs)
Keywords: Amino Acid Sequence/GENETICS Cell Division/PHYSIOLOGY Cell Line, Transformed Cell Transformation, Neoplastic/*GENETICS/PATHOLOGY Gene Expression Regulation, Neoplastic/*PHYSIOLOGY Growth Substances/GENETICS/*PHYSIOLOGY Human Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated/GENETICS Molecular Sequence Data Neoplasms/*GENETICS Receptors, Cell Surface/GENETICS/*PHYSIOLOGY Receptors, Interleukin-2/GENETICS MONOGRAPH REVIEW 912130
M91C4103
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Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
