RESUMO
High-intensity transcription and replication supercoil DNA to levels that can impede or halt these processes. As a potent transcription amplifier and replication accelerator, the proto-oncogene MYC must manage this interfering torsional stress. By comparing gene expression with the recruitment of topoisomerases and MYC to promoters, we surmised a direct association of MYC with topoisomerase 1 (TOP1) and TOP2 that was confirmed in vitro and in cells. Beyond recruiting topoisomerases, MYC directly stimulates their activities. We identify a MYC-nucleated "topoisome" complex that unites TOP1 and TOP2 and increases their levels and activities at promoters, gene bodies, and enhancers. Whether TOP2A or TOP2B is included in the topoisome is dictated by the presence of MYC versus MYCN, respectively. Thus, in vitro and in cells, MYC assembles tools that simplify DNA topology and promote genome function under high output conditions.
Assuntos
DNA Topoisomerases Tipo II/metabolismo , Neoplasias/enzimologia , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transcrição Gênica , Animais , Replicação do DNA , DNA Topoisomerases Tipo I/genética , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo II/genética , DNA de Neoplasias/biossíntese , DNA de Neoplasias/genética , DNA Super-Helicoidal/biossíntese , DNA Super-Helicoidal/genética , Ativação Enzimática , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Células K562 , Complexos Multienzimáticos , Neoplasias/genética , Neoplasias/patologia , Proteínas de Ligação a Poli-ADP-Ribose/genética , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Proto-Oncogênicas c-myc/genética , RatosRESUMO
BACKGROUND: Approximately 6% to 8% of lumbar pain cases, whether associated with radicular pain or not, may be attributed to the presence of piriformis muscle syndrome. Available treatments, among others, include pharmacotherapy, physical therapy, and injections of different substances into the muscle. Various methods have been used to confirm correct needle placement during these procedures, including electromyography (EMG), fluoroscopy, computed tomography (CT), or magnetic resonance imaging (MRI). Ultrasonography (US) has now become a widely used technique and therefore may be an attractive alternative for needle guidance when injecting this muscle. OBJECTIVE: The objective of this study was to assess the reliability of US in piriformis injection of patients with piriformis syndrome. STUDY DESIGN: Feasibility study; 10 patients with piriformis muscle syndrome were injected with botulinum toxin A using a US-guided procedure. Then patients were administered 2 mL iodinated contrast and were then transferred to the CT scanner, where they underwent pelvic and hip imaging to assess intramuscular distribution of the iodinated contrast. SETTING: Multidisciplinary Pain Management Department in Spain. RESULTS: Of all 10 study patients (8 women, 2 men), 9 had intramuscular or intrafascial contrast distribution. Distribution did not go deeper than the piriformis muscle in any of the patients. The absence of contrast (intravascular injection) was not observed in any case. LIMITATIONS: The main limitation of our study is the use of ionizing radiation as confirmation technique. CONCLUSION: Ultrasound-guided puncture may be a reliable and simple procedure for injection of the piriformis muscle, as long as good education and training are provided to the operator. US has a number of advantages over traditional approaches, including accessibility and especially no ionizing radiation exposure for both health care providers and patients.