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M9471076.TXT
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Document 1076
DOCN M9471076
TI Regulation of transcription of the tax transgene and tax-induced genes
in tumor cell lines of the LTR-tax transgenic mouse.
DT 9409
AU Fontes JD; Univ. of California, Davis
SO Diss Abstr Int [B]; 53(9):4501 1993. Unique Identifier : AIDSLINE
ICDB/94690786
AB The LTR-tax transgenic mouse develops peripheral neurofibromas as its
primary pathologic feature. An in vitro cell line (Px-1 cells) derived
from one of these tumors provides an excellent model for the study of
tax-driven neoplasia. Using these cells, the role of tax in the
trans-activation of cellular genes and the transgene itself was studied.
It was determined that tax and activating transcription factor-1 (ATF-1)
are both present in complexes that form between extracts of the Px-1
cell line and viral long terminal repeat (LTR) DNA sequences. Treatment
of Px-1 cells with protein kinase A and protein kinase C activating
agents led to an intensification of these protein-DNA complexes. Using
recombinant proteins, it was also demonstrated that tax increases the
binding of ATF-1 to sequences in the LTR, a result that was also
obtained by treating ATF-1 with protein kinase A in vitro. The
expression of several growth factors was also examined in Px-1 cells.
Potential tax-responsive DNA elements from promoter regions of several
factors were examined for activity in Px-1 cells using reporter
constructs. Only one sequence from granulocyte-macrophage colony
stimulating factor (GMCSF) was found to increase expression over basal
levels. Treatment of Px-1 cells with 8-bromoadenosine 3':5'-cyclic
monophosphate (8Br-cAMP) led to an initial increase in messenger RNA for
GMCSF, followed by a sharp decline. It was demonstrated that tax is
phosphorylated in response to 8Br-cAMP treatment of the Px-1 cells, and
that the previously identified tax-responsive GMCSF enchancer was
responsive to 8Br-cAMP, even though there is no cAMP responsive
enchancer present. (Full text available from University Microfilms
International, Ann Arbor, MI, as Order No. AAD93-02595.)
DE Animal Cyclic AMP-Dependent Protein Kinases/METABOLISM Enzyme
Activation Gene Products, tax/*GENETICS Granulocyte-Macrophage
Colony-Stimulating Factor/GENETICS/ METABOLISM Mice Mice, Transgenic
Protein Kinase C/METABOLISM RNA, Messenger/METABOLISM Repetitive
Sequences, Nucleic Acid *Transcription, Genetic Tumor Cells, Cultured
8-Bromo Cyclic Adenosine Monophosphate/PHARMACOLOGY THESIS
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).