Document 0151
 DOCN  M95B0151
 TI    Cytokine regulation of HIV-1 LTR transactivation in human hepatocellular
       carcinoma cell lines.
 DT    9511
 AU    Hsu ML; Chen SW; Lin KH; Liao SK; Chang KS; Graduate Institute of
       Clinical Medicine, Chang Gung Medical; College, Taoyuan-Hsien, Taiwan,
       Republic of China.
 SO    Cancer Lett. 1995 Jul 20;94(1):41-8. Unique Identifier : AIDSLINE
       MED/95346915
 AB    Human hepatocellular carcinoma (HCC) cell lines, HEP-G2, J5, and
       SK-HEP-1, which differ in their differentiation status, were compared
       for their trans-activating activities after treatment with cytokines or
       12-O-tetradecanoylphorbol-13-acetate (TPA). These cells were transfected
       with a long terminal repeat (LTR) which was derived from human
       immunodeficiency virus type 1 (HIV-1) and ligated to chloramphenicol
       acetyl transferase (CAT) gene. After treatment with interleukin-1 alpha
       (IL-1 alpha), interleukin-6 (IL-6), interferon-gamma (IFN-gamma), or
       TPA, they exhibited various degrees of enhancement of transactivation.
       The well differentiated HEP-G2 cells exhibited the highest degree of
       enhancement with these agents, while the poorly differentiated SK-HEP-1
       cells showed no enhancement with cytokines and slight enhancement with
       TPA. The J5 cells, which were intermediate in their status of
       differentiation, showed a moderate degree of enhancement with cytokines
       and TPA. These results suggest that HCC cells at different stages of
       differentiation may produce different levels of cellular transacting
       factors activated by each of these agents. To map the cytokine response
       elements (CREs) in the HIV-1-LTR, HEP-G2 cells were transfected with
       nested series of 5' deletion mutants of HIV-1-LTR and treated with each
       of these cytokines. It was found that not only the degrees but also the
       patterns of enhancement varied depending upon the presence of positive
       or negative regulatory sequences in HIV-1-LTR, and that the NF-kappa B
       sequence played an important role, either by itself or in conjunction
       with the 5'-proximal response elements (REs) to interact with cellular
       trans-activating factors elicited by the cascade of transduction
       responses to cytokines. Despite the presence of promoters including
       kappa B and IFN-gamma RE as well as IL-6RE sequence in
       HIV-1-LTR-transfected cells, the poorly differentiated SK-HEP-1 cells
       showed no enhancement of transactivation by these cytokines, suggesting
       the lack of receptors or activity of some signal transduction factors
       which are present in well differentiated HEP-G2 and moderately
       differentiated J5 cells.
 DE    Amino Acid Sequence  Base Sequence  Carcinoma,
       Hepatocellular/*ENZYMOLOGY/GENETICS  Chloramphenicol
       Acetyltransferase/GENETICS/*METABOLISM  Enzyme Activation/DRUG EFFECTS
       Gene Expression Regulation, Enzymologic/DRUG EFFECTS  Genetic Vectors
       Human  *HIV Long Terminal Repeat/GENETICS  Interferon Type
       II/*PHARMACOLOGY  Interleukin-1/*PHARMACOLOGY
       Interleukin-6/*PHARMACOLOGY  Liver Neoplasms/*ENZYMOLOGY/GENETICS
       Molecular Sequence Data  *Sequence Deletion  Support, Non-U.S. Gov't
       Tetradecanoylphorbol Acetate/*PHARMACOLOGY  Transfection  Tumor Cells,
       Cultured  Up-Regulation (Physiology)  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).