Enhancer element potentially involved in human survivin gene promoter regulation in lung cancer cell lines.
We have revealed evolutionarily conserved regions in a 4500-bp DNA sequence 5'-adjacent to the survivin (BIRC5) gene. In the transcribed region of the BIRC5 gene we have detected and characterized in detail a 3'-fragment of the CpG island that stimulated in enhancer-like way the gene promoter activity in normal cells and in a number of cancer, in particular lung cancer, cell lines. When added to the initial 1498-bp survivin promoter region, a transcribed DNA fragment of a CpG island approximately twofold enhanced the promoter activity in cancer cells and in normal lung fibroblasts. The observed effect did not depend upon the orientation of the fragment and distances between the fragment and the transcription initiation site. In the case of a heterologous SV40 virus promoter, the effect was less pronounced. In addition to earlier reports, the results provide new information on the BIRC5 gene expression regulation and also demonstrate that this gene exon sequences can play a significant role in BIRC5 gene expression regulation. The data provide another possibility to increase survivin promoter activity without changing its cancer specificity for application in cancer (in particular, lung cancer) gene therapy.
Mityaev
M V
MV
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia. mityaev@humgen.siobc.ras.ru
Kopantzev
E P
EP
Buzdin
A A
AA
Vinogradova
T V
TV
Sverdlov
E D
ED
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D019295:Computational Biology; D017124:Conserved Sequence; D018899:CpG Islands / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D020121:5' Untranslated Regions; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D004247:DNA