Document 0770
 DOCN  M9590770
 TI    HSP70 production and inhibition of cell proliferation in Molt-4 T-cells
       after cell-to-cell transmission of HTLV-I: effect of PGA1.
 DT    9509
 AU    D'Onofrio C; Puglianiello A; Amici C; Faraoni I; Lanzilli G; Bonmassar
       E; Department of Experimental Medicine and Biochemical Sciences,;
       University of Rome Tor Vergata, Italy.
 SO    Leuk Res. 1995 May;19(5):345-56. Unique Identifier : AIDSLINE
       MED/95287634
 AB    Infection with HTLV-I is associated with leukemic transformation of
       mature CD4+ T lymphocytes. PGA1, a powerful inhibitor of tumour cell
       proliferation, can prevent the clonal expansion of HTLV-I-infected cells
       following acute infection of cord blood-derived mononuclear cells. Since
       the antiproliferative effect of PGA1 on HTLV-I transformed, chronically
       infected MT-2 cell line was associated with induction of HSP70, we have
       investigated the effect of PGA1 on cell cycle progression and HSP70
       production in a leukemic T-cell line (Molt-4) shortly after exposure to
       HTLV-I in a cell-to-cell transmission model. Rate of cell proliferation
       and HSP70 expression were studied within one duplication cycle of Molt-4
       cells after exposure to HTLV-I. Growth of both control and virus-exposed
       cultures was inhibited by treatment with PGA1 (4 micrograms/ml) and cell
       cycling was arrested preferentially at the G1/S interphase. Synthesis of
       HSP70 was induced within 3 h by PGA1 in control and virus-exposed Molt-4
       cells and became undetectable from overnight onward, though the protein
       accumulated in the cells. The arrest of growth was observed from
       overnight up to 48 h so that treated cells almost missed one cycle.
       Interestingly, HSP70 transcript and protein persisted at remarkably high
       levels in Molt-4 cells exposed to HTLV-I in the absence of PGA1, showing
       that HSP70 expression can be directly activated during primary infection
       with this human retrovirus. Moreover, in these cocultures, treatment
       with PGA1 or heat shock was not able to increase further the elevated
       level of HSP70 found in untreated cocultures, suggesting that during the
       early period of the virus-transmission phase, HTLV-I could interfere
       with HSP70 induction by other inducers.
 DE    Cell Compartmentation  Cell Division/DRUG EFFECTS  Cell Line  Heat
       Heat-Shock Proteins/*BIOSYNTHESIS/METABOLISM  Human  HTLV-I
       Infections/*METABOLISM/TRANSMISSION  Prostaglandins A/*PHARMACOLOGY
       Support, Non-U.S. Gov't  T-Lymphocytes/METABOLISM/*MICROBIOLOGY  JOURNAL
       ARTICLE

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