Nuclear locations of the c-myc gene and its transcripts (c-myc (T)) have been investigated in relation to nuclear domains involved in RNA synthesis and processing. Transcription of the c-myc gene appears to be linked to the late G(1)- and preferentially to S-phases of the cell cycle. The c-myc gene and its transcripts were positioned non-randomly within the interphase nucleus; additionally, c-myc RNA signals accumulated at nucleoli. Using oligo-probes, designed to exon II and exon III of the c-myc gene, single c-myc (T) was preferentially observed in human carcinoma HT29 and A549 cells. Conversely, human embryonal teratocarcinoma NTERA cells were characterized by the presence of multiple c-myc RNA signals located in both the nucleoli and nucleoplasm. When accumulated at nucleoli, c-myc (T) occupied the periphery of this organelle, though not those associated with the cultivation surface. In HT29 cells, approximately 80% of c-myc (T) co-localized with the RNAP II positive regions, so-called transcription factories. However, in approximately 20% of the cells with c-myc transcripts, the c-myc (T) was released from the site of synthesis, and was not associated with either transcription factories or SC35 domains. In approximately 60% of nuclei with c-myc (T), these signals were located in close proximity to the SC35 regions, but promyelocytic leukaemia bodies were associated with c-myc (T) only in approximately 20% of the nuclei. Taken together, c-myc RNA signals were positioned in the most internal parts of the cell nuclei preferentially associated with the nucleoli. Specific nuclear and nucleolar positioning probably reflects the kinetics of c-myc RNA metabolism.

• MeSH
• buněčné jádro genetika   metabolismus   ultrastruktura   MeSH
• buňky HT-29 MeSH
• exprese genu MeSH
• financování organizované MeSH
• genetická transkripce MeSH
• geny myc MeSH
• lidé MeSH
• lidské chromozomy, pár 8 MeSH
• messenger RNA metabolismus   MeSH
• nádorové buňky kultivované MeSH
• protoonkogenní proteiny c-myc metabolismus   MeSH
• RNA-polymerasa II metabolismus   MeSH
• tkáňová distribuce MeSH
• Check Tag
• lidé MeSH

The transcription factor c-Myc, a key regulator of cellular processes, has long been associated with roles in cell proliferation and apoptosis. This review analyses the multiple functions of c-Myc by examining the different c-Myc isoforms in detail. The impact of different c-Myc isoforms, in particular p64 and p67, on fundamental biological processes remains controversial. It is necessary to investigate the different isoforms in the context of proto-oncogenesis. The current knowledge base suggests that neoplastic lesions may possess the means for self-destruction via increased c-Myc activity. This review presents the most relevant information on the c-Myc locus and focuses on a number of isoforms, including p64 and p67. This compilation provides a basis for the development of therapeutic approaches that target the potent growth arresting and pro-apoptotic functions of c-Myc. This information can then be used to develop targeted interventions against specific isoforms with the aim of shifting the oncogenic effects of c-Myc from pro-proliferative to pro-apoptotic. The research summarised in this review can deepen our understanding of how c-Myc activity contributes to different cellular responses, which will be crucial in developing effective therapeutic strategies; for example, isoform-specific approaches may allow for precise modulation of c-Myc function.

• MeSH
• apoptóza * MeSH
• messenger RNA MeSH
• proliferace buněk MeSH
• protein - isoformy genetika   MeSH
• protoonkogenní proteiny c-myc * genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The general mechanism underlying the tumor suppressor activity of the Hippo signaling pathway remains unclear. In this study, we explore the molecular mechanisms connecting the Hippo signaling pathway with glucose metabolism. We have found that two key regulators of glycolysis, C-MYC and GLUT1, are targets of the Hippo signaling pathway in human leukemia cells. Our results revealed that activation of MST1 by the natural compound shikonin inhibited the expression of GLUT1 and C-MYC. Furthermore, RNAi experiments confirmed the regulation of GLUT1 and C-MYC expression via the MST1-YAP1-TEAD1 axis. Surprisingly, YAP1 was found to positively regulate C-MYC mRNA levels in complex with TEAD1, while it negatively regulates C-MYC levels in cooperation with MST1. Hence, YAP1 serves as a rheostat for C-MYC, which is regulated by MST1. In addition, depletion of MST1 stimulates lactate production, whereas the specific depletion of TEAD1 has an opposite effect. The inhibition of lactate production and cellular proliferation induced by shikonin also depends on the Hippo pathway activity. Finally, a bioinformatic analysis revealed conserved TEAD-binding motifs in the C-MYC and GLUT1 promoters providing another molecular data supporting our observations. In summary, regulation of glucose metabolism could serve as a new tumor suppressor mechanism orchestrated by the Hippo signaling pathway.

• MeSH
• adaptorové proteiny signální transdukční účinky léků   MeSH
• apoptóza účinky léků   genetika   MeSH
• DNA vazebné proteiny účinky léků   MeSH
• fosfoproteiny účinky léků   metabolismus   MeSH
• geny myc účinky léků   MeSH
• hepatocytární růstový faktor MeSH
• jaderné proteiny účinky léků   MeSH
• lidé MeSH
• naftochinony farmakologie   MeSH
• přenašeč glukosy typ 1 metabolismus   MeSH
• proliferace buněk účinky léků   genetika   MeSH
• protoonkogenní proteiny účinky léků   MeSH
• signální transdukce účinky léků   fyziologie   MeSH
• transkripční faktory účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• buňky stromatu metabolismus   MeSH
• finanční podpora výzkumu jako téma MeSH
• imunohistochemie MeSH
• invazivní růst nádoru MeSH
• karcinom in situ metabolismus   MeSH
• keratinocyty metabolismus   MeSH
• lidé MeSH
• nádory děložního čípku metabolismus   MeSH
• protoonkogenní proteiny c-myc fyziologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

• MeSH
• geny myc genetika   MeSH
• lidé MeSH
• mapování chromozomů metody   veterinární   MeSH
• skot MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• zvířata MeSH

• MeSH
• buněčná diferenciace MeSH
• buněčné jádro fyziologie   ultrastruktura   MeSH
• geny myc genetika   MeSH
• HL-60 buňky fyziologie   MeSH
• leukemie genetika   MeSH
• lidé MeSH
• lidské chromozomy, pár 8 genetika   ultrastruktura   MeSH
• Check Tag
• lidé MeSH

Photodynamic therapy (PDT) is based on the tumor-selective accumulation of photosensitizer followed by irradiation with light of an appropriate wavelength. After irradiation and in the presence of oxygen, photosensitizer induces cellular damage. The aim of this study was to evaluate effects of two photosensitizers TMPyP and ClAlPcS2 on cell lines to obtain better insight into their mechanisms of action. We determined cell viability, reactive oxygen species (ROS) generation and changes in expression levels of two important early response genes, C-MYC and C-FOS, on tumor MCF7 (human breast adenocarcinoma) and G361 (human melanoma) cell lines and non-tumor BJ cell line (human fibroblast) after photodynamic reaction with TMPyP and ClAlPcS2 as photosensitizers. In addition TMPyP and ClAlPcS2 cellular uptake and clearance and antioxidant capacity of the mentioned cell lines were investigated. We found appropriate therapeutic doses and confirmed that both tested photosensitizers are photodynamically efficient in treatment used cells in vitro. TMPyP is more efficient; it had higher ROS production and toxicity after irradiation by intermediate therapeutic doses than ClAlPcS2. We revealed that both TMPyP and ClAlPcS2-PDT increased C-FOS expression on tumor cell lines (G361 and MCF7), but not on non-tumor BJ cell line. Conversely, both TMPyP and ClAlPcS2-PDT decreased C-MYC expression on non-tumor BJ cell line but not on tumor cell lines. As first we tested these photosensitizers in such extent and we believe that it can help to better understand mechanisms of PDT and increase its efficiency and applicability.

• MeSH
• antioxidancia metabolismus   MeSH
• fotochemoterapie MeSH
• fotosenzibilizující látky chemie   terapeutické užití   toxicita   MeSH
• indoly chemie   terapeutické užití   toxicita   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   MeSH
• organokovové sloučeniny chemie   terapeutické užití   toxicita   MeSH
• porfyriny chemie   terapeutické užití   toxicita   MeSH
• protoonkogenní proteiny c-fos metabolismus   MeSH
• protoonkogenní proteiny c-myc metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• světlo MeSH
• upregulace účinky léků   účinky záření   MeSH
• viabilita buněk účinky léků   účinky záření   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In last few years, numerous groups of proteins participating in the regulation of cell proliferation, differentiation and death during ontogenesis have been described. In this study we compared the occurrence of Bcl-2, p53 and myc protein families with the level of proliferative activity and apoptosis during development of duodenal epithelium. Paraffin embedded tissues of eight human embryos and foetuses aged from the 6th-18th week of IUD were used. For the detection of apoptotic cells the TUNEL method was performed, the proliferative marker PCNA and all the proteins studied were detected by means of indirect three-step immunohistochemical method. In the 6th and 8th week of intrauterine development we observed isolated TUNEL positive epithelial cells only and this was accompanied by the disperse presence of PCNA as well as by all the studied proteins: Bcl-2, Bax, Bcl-XL, c-myc, N-myc, p53, p63 and p73. In the early foetal period of duodenal development we registered changes in PCNA and TUNEL positivity in accordance with the constitution of the stem cell pool on base of villi, where more numerous Bcl-2 positive cells were also found. The separation of primitive crypts and villi was not accompanied by any differences in distribution of Bax, Bcl-XL, c-myc, N-myc, p63 and p73 proteins between those compartments: all the studied proteins showed dispersed character. P53 rapidly decreased in this period. In the 18th week of intrauterine development the balance between proliferation in crypts and apoptosis of villi epithelium was well established and no p53 positive cells were found. In the presence of Bcl-2, Bax, Bcl-XL, p63 and p73 we did not find any dramatic changes. The myc proteins were restricted within the epithelium of the Lieberkuhn crypts only.

• MeSH
• apoptóza MeSH
• duodenum cytologie   embryologie   metabolismus   MeSH
• embryo savčí metabolismus   MeSH
• epitel embryologie   metabolismus   MeSH
• imunohistochemie MeSH
• lidé MeSH
• nádorový supresorový protein p53 analýza   MeSH
• proliferace buněk MeSH
• protoonkogenní proteiny c-bcl-2 analýza   MeSH
• protoonkogenní proteiny c-myc analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Kaposi sarcoma-associated herpesvirus is associated with two lymphoproliferative disorders, primary effusion lymphoma (PEL) and Castleman disease. In PEL, Kaposi sarcoma-associated herpesvirus is present in a latent form expressing only few viral genes. Among them is a viral homologue of cellular interferon regulatory factors, vIRF-3. To study the role of vIRF-3 in PEL lymphomagenesis, we analyzed the interaction of vIRF-3 with cellular proteins. Using yeast two-hybrid screen, we detected the association between vIRF-3 and c-Myc suppressor, MM-1alpha. The vIRF-3 and MM-1alpha interaction was also demonstrated by glutathione S-transferase pulldown assay and coimmunoprecipitation of endogenous vIRF-3 and MM-1alpha in PEL-derived cell lines. Overexpression of vIRF-3 enhanced the c-Myc-dependent transcription of the gene cdk4. Addressing the molecular mechanism of the vIRF-3-mediated stimulation, we demonstrated that the association between MM-1alpha and c-Myc was inhibited by vIRF-3. Furthermore, the recruitment of vIRF-3 to the cdk4 promoter and the elevated levels of the histone H3 acetylation suggest the direct involvement of vIRF-3 in the activation of c-Myc-mediated transcription. These findings indicate that vIRF-3 can effectively stimulate c-Myc function in PEL cells and consequently contribute to de-regulation of B-cell growth and differentiation.

• MeSH
• financování organizované MeSH
• genová knihovna MeSH
• interferonové regulační faktory metabolismus   MeSH
• interferonový regulační faktor 3 metabolismus   MeSH
• lidé MeSH
• lidský herpesvirus 8 metabolismus   MeSH
• nádorové buněčné linie MeSH
• primární efuzivní lymfom metabolismus   MeSH
• protoonkogenní proteiny c-myc metabolismus   MeSH
• techniky dvojhybridového systému MeSH
• virové proteiny metabolismus   MeSH
• Check Tag
• lidé MeSH

• MeSH
• cyklin D1 diagnostické užití   genetika   MeSH
• dospělí MeSH
• geny myc genetika   MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• nádory prsu farmakoterapie   sekundární   terapie   MeSH
• prognóza MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• abstrakt z konference MeSH