RESUMO
The family of genes containing C2H2 zinc finger domains, which has more than 700 members, is one of the largest in the genome. Of particular interest are C2H2 genes with potential tissue-specific transcription, which determine the functional properties of individual cell types, including those associated with pathological processes. The aim of this work was to identify C2H2 family genes with tissue-specific transcription and analyze changes in their activity during tumor progression. To search for these genes, we used four databases containing data on gene transcription in human tissues obtained by RNA-Seq analysis. The analysis showed that, although the major part of the C2H2 family genes is transcribed in virtually all tissues, a group of genes has tissue-specific transcription, with most of the transcripts being found in the testis. After having compared all four databases, we identified nine such genes. The testis-specific transcription was confirmed for two of them, namely ZBTB32 and ZNF473, using quantitative PCR of cDNA samples from different organs. A decrease in ZBTB32 and ZNF473 transcription levels was demonstrated in germ cell tumors. The studied genes can serve as candidate markers in germ cell tumors.
RESUMO
An artificial double tandem tumor-specific promoter based on survivin and human telomerase reverse transcriptase gene promoters was constructed. Studies in in vitro and ex vivo therapeutic systems showed that the designed promoter exhibits a high activity in tumor cells, which is comparable to the activity of the CMV constitutive promoter.
Assuntos
Citomegalovirus/genética , Terapia Genética , Proteínas Inibidoras de Apoptose/genética , Neoplasias/genética , Neoplasias/terapia , Regiões Promotoras Genéticas , Linhagem Celular Tumoral , Humanos , Neoplasias/patologia , SurvivinaRESUMO
In this study, we evaluated the antitumor activity of a gene therapy complex in which the tumor-specific control of the expression of the effector suicide gene FCU1 was performed using a two-vector system based on the site-specific Cre-LoxP recombinase system. The complex of interest showed a high therapeutic potential in a mouse colon adenocarcinoma model.
Assuntos
Adenocarcinoma , Neoplasias do Colo , Genes Transgênicos Suicidas , Vetores Genéticos , Integrases , Neoplasias Experimentais , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/terapia , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/terapia , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Integrases/genética , Integrases/metabolismo , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/terapiaRESUMO
Here we directly compared gene expression profiles in human esophageal squamous cell carcinomas and in human fetal esophagus development. We used the suppression subtractive hybridization technique to subtract cDNAs prepared from tumor and normal human esophageal samples. cDNA sequencing and reverse transcription polymerase chain reaction (RT-PCR) analysis of RNAs from human tumor and the normal esophagus revealed 10 differentially transcribed genes: CSTA, CRNN, CEACAM1, MAL, EMP1, ECRG2, and SPRR downregulated, and PLAUR, SFRP4, and secreted protein that is acidic and rich in cysteine upregulated in tumor tissue as compared with surrounding normal tissue. In turn, genes up- and downregulated in tumor tissue were down- and upregulated, respectively, during development from the fetal to adult esophagus. Thus, we demonstrated that, as reported for other tumors, gene transcriptional activation and/or suppression events in esophageal tumor progression were opposite to those observed during development from the fetal to adult esophagus. This tumor 'embryonization' supports the idea that stem or progenitor cells are implicated in esophageal cancer emergence.
