Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin inhibits the hepatic transcription of insulin-like growth factor binding protein-1 (IGFBP-1). In the present studies, human HEP G2 hepatoma cells were transiently transfected with human IGFBP-1 gene promoter constructs in order to identify cis elements and trans-acting factors that confer the insulin effect. Transfections of IGFBP-1 promoter deletion constructs localized an insulin responsive element (IRE) between approximately 140- and approximately 103-base pair (bp) 5' to the mRNA capsite. This region contains a 25-bp sequence which is 100% conserved in the rat IGFBP-1 promoter and which has two AT-rich, 8-bp elements exhibiting dyad symmetry. Site-directed mutagenesis of both elements in the same 1205-bp IGFBP-1 promoter construct abolished the inhibitory effect of insulin on promoter activity. Also, the native but not the mutant IGFBP-1 IRE conferred the inhibitory effect of insulin to the heterologous thymidine kinase promoter. Gel mobility shift assays identified a DNA binding activity which specifically binds the native IGFBP-1 IRE and which is not altered by prior insulin treatment. The IGFBP-1 IRE sequence is similar to those of functionally mapped IREs from other gene promoters, suggesting that this common IRE and the protein(s) which it binds confer the insulin effect to a number of insulin-sensitive genes.
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PMID:Identification of an insulin-responsive element in the promoter of the human gene for insulin-like growth factor binding protein-1. 768 22

The adenomatous polyposis coli (APC) or beta-catenin genes are frequently mutated in colorectal cancers, leading to activation of downstream genes with beta-catenin/T-cell factor (Tcf)-responsive promoters. We have developed a gene therapy approach selectively targeting colorectal cancer cells in which beta-catenin/Tcf4 pathway is activated by using a recombinant adenovirus AdTOP-CMV-TK, which carries a herpes simplex virus thymidine kinase gene (HSV TK) under the control of a beta-catenin/Tcf-response promoter linking to a minimum CMV promoter. AdTOP-CMV-TK and ganciclovir (GCV) treatment significantly suppressed the growth of human DLD-1 colon cancer cells in nude mice. Furthermore, no significant tumor suppression effect was observed in human hepatoma cell line SK-HEP-1, in which the beta-catenin/Tcf pathway is not activated, as a control experiment. In summary, we demonstrated the selective targeting of colorectal cancers with activated beta-catenin by AdTOP-CMV-TK and GCV treatment in animal models, as well as its therapeutic potential for colon cancer metastasized to liver.
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PMID:The suppression of colon cancer cell growth in nude mice by targeting beta-catenin/TCF pathway. 1244 97