Document 0819
 DOCN  M95A0819
 TI    The HIV-1 TAT protein induces the expression and extracellular
       appearance of acidic fibroblast growth factor.
 DT    9510
 AU    Opalenik SR; Shin JT; Wehby JN; Mahesh VK; Thompson JA; Department of
       Surgery, School of Medicine, University of Alabama; at Birmingham 35294,
       USA.
 SO    J Biol Chem. 1995 Jul 21;270(29):17457-67. Unique Identifier : AIDSLINE
       GENBANK/U26456
 AB    Mounting experimental evidence suggests that the TAT protein, released
       from human immunodeficiency virus-1 (HIV-1)-infected inflammatory cells,
       may genetically reprogram targeted cells within a localized environment
       to develop highly vascularized tumors of mesenchymal origin. The
       fibroblast growth factor (FGF) family of polypeptides has gained general
       acceptance as initiators of angiogenesis and functions as potent
       mitogens for mesoderm-derived cells. To evaluate a potential biological
       relationship between TAT and acidic FGF (FGF-1), primary murine
       embryonic fibroblasts either were transfected with the viral
       transactivator or were transduced (retrovirally mediated) with a
       secreted, chimeric form of the human polypeptide growth factor, human
       stomach tumor/Kaposi's sarcoma (hst/KS)FGF-1. Reverse
       transcriptase-polymerase chain reaction, Western blotting, in situ
       immunohistochemical, heparin affinity, DNA synthesis, and transient
       transfection techniques were used to confirm expression, localization,
       and functionality of the transgenes. Both transfected and transduced
       cells constitutively expressing either TAT or (hst/KS)FGF-1 adopted a
       transformed phenotype, maintained aggressive growth behavior, and
       demonstrated both induction of FGF-specific phosphotyrosyl proteins and
       nuclear association of FGF-1 and FGF-1 receptor. Increased levels of
       endogenous, murine FGF-1 mRNA (reverse transcriptase-polymerase chain
       reaction) and protein (immunoblot analysis) were apparent in both
       (hst/KS)FGF-1- and TAT-transformed cells. Medium conditioned by
       (hst/KS)FGF-1-transduced cells contained steady-state levels of
       biologically active FGF-1 which exhibited a representative molecular
       weight. Limited sodium dodecyl sulfate-polyacrylamide gel
       electrophoretic analysis of the conditioned medium from TAT-transformed
       cells demonstrated the appearance of FGF-1 as latent, high molecular
       weight complexes requiring reducing agents to activate full biological
       activity. Collectively, these results suggest that TAT induces the
       expression and secretion of FGF-1, which may be potentially relevant to
       the pathophysiological development of AIDS-Kaposi's sarcoma.
 DE    Acquired Immunodeficiency Syndrome/ETIOLOGY  Amino Acid Sequence  Animal
       Base Sequence  Cells, Cultured  Fibroblast Growth Factor,
       Acidic/*BIOSYNTHESIS/GENETICS  Gene Products, tat/*PHYSIOLOGY
       HIV-1/*GENETICS  Mice  Molecular Sequence Data  Phosphorylation  RNA,
       Messenger/ANALYSIS  Support, U.S. Gov't, P.H.S.  Tyrosine/METABOLISM
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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