Document 0969 DOCN M9460969 TI Characterization of a transcriptional activator in the envelope gene of mouse mammary tumor virus. DT 9406 AU Miller CL; Univ. of Alberta, Canada SO Diss Abstr Int [B]; 54(3):1387 1993. Unique Identifier : AIDSLINE ICDB/94697102 AB Mouse mammary tumor virus (MMTV) is the causative agent of mammary carcinomas in certain mouse strains. There is also evidence indicating that it may be associated with the development of T lymphomas. Transcription of the complete MMTV proviral genome in mouse cells is controlled by a strong promoter in its long terminal repeat (LTR). In the mouse T lymphoma cell line EL4.E1, there is a second, activation-dependent, transcriptional activator sequence within the MMTV envelope (env) gene. Phorbol ester treatment of EL4.E1 cells generates a transcript initiating within the env gene, which includes the open reading frame gene of the 3' LTR. I have isolated and characterized a segment of the MMTV env gene (called META for MMTV env transcriptional activator). META was linked to the chloramphenicol acetyltransferase (CAT) gene for use in transient-expression assays. META induced activation-dependent, T lymphocyte-specific expression of the CAT gene. It was active in mouse and human T helper cell lines but not in other cell types. META activity was dependent on activation of the T helper cell line with the same stimuli which induced cytokine production and its activity was suppressible by the immunosuppressive drug, Cyclosporin A. META has been isolated from EL4.E1 cells, from a T cell hybridoma, and from BALB/c spleen cells. It was also demonstrated that a portion of META acts as an inducible, orientation-independent, CsA-sensitive enhancer when linked to a heterologous promoter. A model for the potential involvement of META in MMTV-induced T lymphomagenesis is presented. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AADNN-77372) DE Animal Chloramphenicol Acetyltransferase/GENETICS Cyclosporine/PHARMACOLOGY Gene Expression Gene Products, env/*GENETICS Lymphocyte Transformation Lymphoma, T-Cell/*GENETICS Mammary Tumor Viruses, Mouse/DRUG EFFECTS/*GENETICS Mice Promoter Regions (Genetics) Repetitive Sequences, Nucleic Acid T-Lymphocytes, Helper-Inducer/IMMUNOLOGY *Trans-Activation (Genetics) THESIS SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).