Tissue-specific posttranscriptional downregulation of expression of the S100A4(mts1) gene in transgenic animals.
The S100A4(mts1) is a gene associated with generation of metastatic disease. In order to analyze the consequences of alteration of the pattern of expression of the S100A4(mts1) gene we obtained strains of transgenic mice bearing the S100A4(mts1) gene under the control of a ubiquitous and constitutive 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) gene promoter. In transgenic animals the expression of the transgene RNA was detected in all organs, but only some of the organs showed elevated levels of the protein. Expression of the S100A4(Mts1) protein was downregulated in the organs that normally do not express the gene in the wild-type animal. The transgene RNA is detected in the polysomes indicating that it could be translated into the S100A4(Mts1) protein. The specificity of the S100A4(Mts1) protein expression is determined by a complex mechanism including regulation of translation and/or posttranslational degradation.
Ambartsumian
N
N
Danish Cancer Society, Department of Molecular Cancer Biology, Institute of Cancer Biology, Copenhagen, Denmark. na@cancer.dk
Klingelhöfer
J
J
Grigorian
M
M
Karlstrøm
O
O
Sidenius
N
N
Georgiev
G
G
Lukanidin
E
E
D000818:Animals; D001921:Brain / Q000378:metabolism; D005786:Gene Expression Regulation; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis* / Q000235:genetics; D019076:Transgenes
D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D006903:Hydroxymethylglutaryl CoA Reductases