RESUMO
Probable relationship between modulation of gene expression by simple repeating sequences and competition capacity of the host was studied. (AC)20 repeat can both stimulate and inhibit the expression of chloramphenicol acetyl transferase gene expression in E. coli cells depending on this gene's position. Modulation of the gene expression by simple (AC)20 repeat and competitive capacity of bacteria containing this plasmid are closely related.
Assuntos
Cloranfenicol O-Acetiltransferase/genética , Escherichia coli/metabolismo , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica , Repetições MinissatélitesRESUMO
After the accident at the Chernobyl nuclear power plant, a considerable increase in the incidence of thyroid cancer among children in Belarus was observed. In the present study, the frequency of the c-ret protooncogene rearrangements in samples of thyroid carcinomas resected and diagnosed in 1998 from individuals in Belarus was investigated. The ret/PTC1 oncogene was detected in 19% of the samples, and the ret/PTC3r1 oncogene, in 14%. The number of ret/PTC1 rearrangements observed in tumor cells from the patients whose age at the time of the accident was from 1 to 10 years, was greater compared to those whose age at the time was from 10 to 20 years, irrespective of the year of surgery (1996 or 1998). The majority of the patients with ret/PTC3r1 rearrangements lived in Gomel oblast, which was contaminated by the Chernobyl meltdown.
Assuntos
Rearranjo Gênico , Neoplasias Induzidas por Radiação/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Oncogênicas/genética , Centrais Elétricas , Liberação Nociva de Radioativos , Neoplasias da Glândula Tireoide/genética , Fatores de Transcrição , Criança , Humanos , Coativadores de Receptor Nuclear , Proteínas Tirosina Quinases , Neoplasias da Glândula Tireoide/etiologia , UcrâniaRESUMO
After the Chernobyl accident in 1986, there was a significant increase in the incidence of papillary thyroid carcinoma in fallout-exposed children from Belarus. We studied the p53 gene from 24 papillary thyroid carcinoma cases presenting in 1996. All subjects lived in contaminated regions of Belarus at the time of the accident and were under age 20 when exposed to fallout. Exons 5 through 9 of p53 were amplified from genomic tumor DNA using the polymerase chain reaction (PCR). The PCR products were analyzed by direct DNA sequencing using an automated sequencer. Five cases each exhibited two molecular alterations within exon 5. Alterations were confirmed by sequencing in both directions. One alteration, involving codon 167 (CAG-->CAT) in all five cases, resulted in the substitution of HIS for GLN. The second alteration, involving codon 183 (TCA-->TGA) in all five cases, resulted in a premature termination codon. Leukocyte DNA from each of the positive cases was analyzed and found to contain only wild-type p53 sequence. These results suggest that mutations involving codons 167 and 183 in the p53 locus are important in the pathogenesis of a subset (21%) of radiation-induced papillary thyroid carcinomas from Belarus.
Assuntos
Carcinoma Papilar/genética , Códon/genética , Mutação/genética , Reatores Nucleares , Liberação Nociva de Radioativos , Neoplasias da Glândula Tireoide/genética , Proteína Supressora de Tumor p53/genética , Adolescente , Adulto , Sequência de Bases/genética , Criança , DNA de Neoplasias/genética , Feminino , Humanos , Masculino , Dados de Sequência Molecular , República de Belarus , UcrâniaRESUMO
According to some published reports, simple repeats can modulate gene transcription. The ability of (AC)n and (AT)n sequences to modulate gene expression in E. coli was investigated. These repeats were inserted in the leader sequence, in its 3' uncoding region, and in both these sites. When simple sequences were inserted in the leader sequence, gene expression was the highest for constructions containing 40 bp insertion. An increase in the insertion length led to a decrease in the gene expression. The (AC)20 sequence insertions in a 3' uncoding site of cat gene did not notably change its expression. Gene expression was much more modified by inserting the simple sequences on both sites of cat gene. Cat gene expression depended on the ratio of simple sequence lengths in its 5' and 3' uncoding sites. It was the highest when (AC)n sequence in the gene leader sequence or its 3' uncoding region was 40 bp. Gene expression modulation by simple sequence is assumed to be associated with the DNA lability increase.
Assuntos
Cloranfenicol O-Acetiltransferase/genética , Escherichia coli/genética , Regulação Enzimológica da Expressão Gênica , Sequências Repetitivas de Ácido Nucleico , Regiões 3' não Traduzidas/genética , Regulação Bacteriana da Expressão Gênica , Plasmídeos , TransfecçãoRESUMO
The peculiarities of alternative CD44 mRNA splicing in thyroid cancer tissue of children from radiocontaminated areas was investigated. CD44 gene expression in thyroid cancer tissues of children exposed to radiation resembled that in spontaneously emerged cancers. It was concluded that CD44 gene expression is not the primary target of radioactive irradiation. Probably, the CD44 mRNA splicing deregulation is the consequence of cancer.
Assuntos
Carcinoma Papilar/genética , Regulação Neoplásica da Expressão Gênica/genética , Receptores de Hialuronatos/genética , Oncogenes/genética , Neoplasias da Glândula Tireoide/genética , Processamento Alternativo/genética , Processamento Alternativo/efeitos da radiação , Sequência de Bases , Criança , Primers do DNA , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Receptores de Hialuronatos/efeitos da radiação , Dados de Sequência Molecular , Oncogenes/efeitos da radiação , Reação em Cadeia da Polimerase/métodos , Centrais Elétricas , RNA Mensageiro/genética , RNA Mensageiro/efeitos da radiação , Liberação Nociva de Radioativos , República de Belarus , Glândula Tireoide/efeitos da radiação , UcrâniaRESUMO
After the Chernobyl accident in 1986, there was a significant increase in the incidence of papillary thyroid cancer in fallout-exposed children from Belarus. Radiation-induced rearrangements of chromosome 10 involving the c-ret proto-oncogene have been implicated in the pathogenesis of these cancers. The ret/PTC3r1 rearrangement was the most prevalent molecular lesion identified in post-Chernobyl papillary thyroid cancers arising in 1991 and 1992. We identified the ret/PTC1 rearrangement in 29% of 31 papillary thyroid cancers presenting in Belarus in 1996. In the present report, we examined 14 cases from this series (plus 1 additional case) and found a ret/PTC3r1 rearrangement in only 1 (7%). The prevalence of ret/PTC3r1 in this series is significantly lower than previously reported (p = 0.0006, Fisher exact test). This result suggests a switch in the ratio of ret/PTC3 to ret/PTC1 rearrangements in late (1996) versus early (1991-1992) post-Chernobyl papillary thyroid cancers.
Assuntos
Carcinoma Papilar/genética , Proteínas de Drosophila , Rearranjo Gênico/genética , Centrais Elétricas , Proteínas Proto-Oncogênicas/genética , Liberação Nociva de Radioativos , Receptores Proteína Tirosina Quinases/genética , Neoplasias da Glândula Tireoide/genética , Sequência de Bases/genética , Feminino , Frequência do Gene , Humanos , Masculino , Dados de Sequência Molecular , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-ret , República de Belarus , UcrâniaRESUMO
An increase in the incidence of papillary thyroid cancer has been documented in individuals exposed to Chernobyl fallout in 1986. Experiments using cultured human cells have suggested that radiation can induce the ret/PTC1 rearrangement involving the ret proto-oncogene. To test the hypothesis that the ret/PTC1 rearrangement is involved in the pathogenesis of Chernobyl-associated papillary thyroid carcinomas, we studied a panel of 31 cases from Belarus. All individuals lived in fallout-contaminated oblasts (regions) of Belarus at the time of the accident: Gomel (n = 13), Brest (n = 12), Minsk (n = 4), and Grodno (n = 2). All were under age 20 at the time of the accident; 20 were born between 1982 and 1986. Individual thyroid radiation doses were estimated at 1.1 to 110 rem. Patients underwent surgery in Minsk in 1996. Fifteen patients had locally advanced disease (stage T4). The majority had regional lymph node involvement (stage N1, n = 27). There were no distant metastases. Surgical specimens were frozen at -80 degrees C, RNA was extracted and cDNA prepared. The polymerase chain reaction (PCR) was performed with specific primers for ret/PTC1, and c-ret and GAPDH as controls. Controls were positive in all 31 cases. Nine cases yielded a positive PCR product for the ret/PTC1 rearrangement (29%). Thus, the ret/PTC1 rearrangement is a feature of some Chernobyl-associated papillary thyroid cancers, and is one possible mechanism involved in the pathogenesis of these cancers.