Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Regulation of transcription of the tax transgene and tax-induced genes in tumor cell lines of the LTR-tax transgenic mouse.
Diss Abstr Int [B]; 53(9):4501 1993. Unique Identifier : AIDSLINE ICDB/94690786 Fontes JD; Univ. of California, Davis
Abstract:
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.)
Keywords: 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 Repetitive Sequences, Nucleic Acid RNA, Messenger/METABOLISM *Transcription, Genetic Tumor Cells, Cultured 8-Bromo Cyclic Adenosine Monophosphate/PHARMACOLOGY THESIS
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
