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
• 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
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• messenger RNA MeSH
• MYC protein, human MeSH Prohlížeč
• protoonkogenní proteiny c-myc MeSH
• RNA-polymerasa II MeSH

Using sequential RNA-DNA fluorescence in situ hybridization, the nuclear arrangement of both the active and inactive c-myc gene as well as its transcription was investigated in colon cancer HT-29 cells induced to differentiate into enterocytes. Cytogenetic studies revealed the presence of two chromosomes 8 in HT-29 cells, of which the one containing c-myc gene amplicons was substantially larger and easily distinguished from the normal chromosome. This observation enabled detection of both activity and nuclear localization of c-myc genes in single cells and in individual chromosome territories. Similar transcriptional activity of the c-myc gene was observed in both the normal and derivative chromosome 8 territories showing no influence of the amplification on the c-myc gene expression. Our experiments demonstrate strikingly specific nuclear and territorial arrangements of active genes as compared with inactive ones: on the periphery of their territories facing to the very central region of the cell nucleus. Nuclear arrangement of c-myc genes and transcripts was conserved during cell differentiation and, therefore, independent of the level of differentiation-specific c-myc gene expression. However, after the induction of differentiation, a more internal territorial location was found for the single copy c-myc gene of normal chromosome 8, while amplicons conserved their territorial topography.

• MeSH
• adenokarcinom metabolismus   MeSH
• azidy MeSH
• buněčná diferenciace MeSH
• buněčné jádro MeSH
• enterocyty fyziologie   MeSH
• genetická transkripce MeSH
• genová dávka MeSH
• geny APC MeSH
• geny myc * MeSH
• lidé MeSH
• lidské chromozomy, pár 8 metabolismus   MeSH
• nádorové biomarkery analýza   MeSH
• nádorové buněčné linie MeSH
• nádory tračníku metabolismus   MeSH
• proliferace buněk MeSH
• protoonkogenní proteiny c-myc metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• azidy MeSH
• hydroxysuccinimidyl-4-azidobenzoate MeSH Prohlížeč
• nádorové biomarkery MeSH
• protoonkogenní proteiny c-myc MeSH

In two tumour sublines (T.wt/BL and T.wt/Bc), established from mammary adenocarcinomas caused by mouse polyoma (Py) infection of nu/nu mice, integration of polyomavirus DNA sequences into the c-myc gene locus was mapped. A complete Py genome was found to be integrated just upstream from the c-myc gene in T.wt/BL cell line, while only a part of the early Py region coding for the early proteins was inserted in the chromosomal DNA of T.wt/Bc cells. An interference of Py sequences with the regulation of c-myc gene expression gives further significance to a Py-derived tumour system that appears to be similar to some human mammary cancers in the modifications of c-myc expression. Both cell lines were found to produce truncated large T antigen and entire middle and small T antigens. In addition, production of VP1 protein was observed in the T.wt/BL cell line. The integration of polyomavirus sequences and/or expression of viral proteins caused an elevation of c-myc expression. The level of the c-myc expression was higher in both tumour cell lines in comparison with control normal murine mammary gland (NMuMG) lines, but substantially lower than in NMuMG cells infected with polyomavirus. Possible co-operation of Py proteins with c-Myc was examined. Through GST fusion protein pull-down experiments, we evidenced, that c-Myc forms a complex with the common part of the Py early antigens in the two tumour cell lines. Co-localisation of the c-myc and LT was observed in cells overexpressing c-Myc and LT.

• MeSH
• adenokarcinom genetika   virologie   MeSH
• antigeny transformující polyomavirové genetika   metabolismus   MeSH
• DNA nádorová analýza   MeSH
• DNA virů analýza   MeSH
• experimentální nádory mléčných žláz genetika   virologie   MeSH
• geny myc fyziologie   MeSH
• glutathiontransferasa metabolismus   MeSH
• integrace viru * MeSH
• lidé MeSH
• mléčné žlázy lidské fyziologie   virologie   MeSH
• myši MeSH
• Polyomavirus genetika   MeSH
• protoonkogenní proteiny c-myc genetika   metabolismus   MeSH
• virová transformace buněk MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny transformující polyomavirové MeSH
• DNA nádorová MeSH
• DNA virů MeSH
• glutathiontransferasa MeSH
• protoonkogenní proteiny c-myc MeSH

A high level of c-myc gene expression was found to be a constant feature of v-src transformation. The c-myc gene product was analyzed in quail embryo cells transformed by different mutants of Rous sarcoma virus (RSV) that were temperature-sensitive with respect to various parameters of v-src function. The high-level expression of c-myc proved not to be temperature-sensitive: at both permissive (35 degrees C) and non-permissive (41 degrees C) temperatures, the same high levels of c-myc gene product were found for all RSV mutants tested. This result, in agreement with earlier evidence for a v-src-induced proliferative stimulus which was unaffected by ts mutants at the non-permissive temperature, shows that certain v-src functions have not yet been fully characterized.

• MeSH
• aktivace transkripce MeSH
• Coturnix embryologie   mikrobiologie   MeSH
• fenotyp MeSH
• geny myc genetika   MeSH
• protoonkogenní proteiny c-myc genetika   metabolismus   MeSH
• ptačí sarkom genetika   mikrobiologie   MeSH
• regulace exprese virových genů genetika   MeSH
• regulace genové exprese u nádorů genetika   MeSH
• senzitivita a specificita MeSH
• teplota MeSH
• virová transformace buněk genetika   MeSH
• viry ptačího sarkomu genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• protoonkogenní proteiny c-myc 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.

• Klíčová slova
• MycHex1, c-Myc S, c-Myc locus structure, mrtl, p64 isoform, p67 isoform,
• 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
• Názvy látek
• messenger RNA MeSH
• protein - isoformy MeSH
• protoonkogenní proteiny c-myc * 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.

• Klíčová slova
• C-MYC, GLUT1, Glycolysis, Hippo, TEAD1, YAP1,
• 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 proteiny YAP MeSH
• signální transdukce účinky léků   fyziologie   MeSH
• transkripční faktory TEA domény MeSH
• transkripční faktory účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• DNA vazebné proteiny MeSH
• fosfoproteiny MeSH
• hepatocytární růstový faktor MeSH
• jaderné proteiny MeSH
• macrophage stimulating protein MeSH Prohlížeč
• naftochinony MeSH
• přenašeč glukosy typ 1 MeSH
• protoonkogenní proteiny MeSH
• shikonin MeSH Prohlížeč
• signální proteiny YAP MeSH
• SLC2A1 protein, human MeSH Prohlížeč
• TEAD1 protein, human MeSH Prohlížeč
• transkripční faktory TEA domény MeSH
• transkripční faktory MeSH
• YAP1 protein, human MeSH Prohlížeč

The c-myc gene plays an essential role in the regulation of the cell cycle and differentiation. Therefore, changes of the c-myc positioning during differentiation are of great interest. As a model system of cell differentiation, the HL-60 and U-937 human leukemic cell lines were used in our experiments. These cells can be induced to differentiation into granulocytes that represent one of the pathways of blood cell maturation. In this study, changes of the topographic characteristics of the c-myc gene (8q24), centromeric region of chromosome 8 and chromosome 8 domain during differentiation of HL-60 and U-937 cells were detected using fluorescence in-situ hybridisation (FISH). FISH techniques and fluorescence microscopy combined with image acquisition and analysis (high-resolution cytometry) were used in order to detect the topographic features of nuclear chromatin. Increased centre of nucleus-to-gene and gene-to-gene distances of c-myc genes, centromeric region of chromosome 8 and chromosome 8 domains were found early after the induction of granulocytic differentiation by dimethyl sulfoxide (DMSO) or retinoic acid (RA); the size of the chromosome 8 domains was rapidly reduced. In differentiated cells, c-myc is located at greater distances from the centromeric regions of chromosome 8. These results support the idea that relocation of the c-myc gene to the nuclear periphery and the condensation of the chromosome 8 domain might be associated with the c-myc gene expression due to common kinetics during granulocytic differentiation.

• MeSH
• buněčná diferenciace MeSH
• buněčné jádro genetika   metabolismus   MeSH
• buněčný cyklus MeSH
• centromera genetika   metabolismus   MeSH
• geny myc genetika   MeSH
• granulocyty cytologie   metabolismus   MeSH
• HL-60 buňky MeSH
• hybridizace in situ fluorescenční MeSH
• leukemie genetika   patologie   MeSH
• lidé MeSH
• lidské chromozomy, pár 8 genetika   metabolismus   MeSH
• makrofágový antigen 1 metabolismus   MeSH
• nádorové buňky kultivované cytologie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• makrofágový antigen 1 MeSH

The biological behaviour of precancerous and early stages of uterine cervix carcinoma is not always easily predictable. It is important therefore to identify new biological markers which could more reliably predict the evolution of the disease or provide important therapeutic targets. To establish the role of the proto-oncogene c-myc in uterine cervix tumorigenesis, we examined 96 tissue samples of different degrees of cervical intraepithelial neoplasia (CIN1-CIN 3), in situ (CIS) or invasive squamous cell carcinoma (ISCC) and control cases. Indirect immunohistochemical techniques were used to detect the c-myc expression. Significantly higher levels of Myc protein were found in keratinocytes of high-grade dysplasias in comparison to low-grade dysplasias and control cases. There was no difference between low-grade CIN and a control group of patients. The same significant changes between above mentioned groups were seen in surrounding stromal cells (fibrocytes, fibroblasts, some endothelial cells and lymphocytes). We confirm that expression of c-Myc protein is increased not only in uterine cervix cancer but also in the premalignant lesions. Problem for discussion seems there for whether increased Myc expression in stromal cells might create a more tumor promoting microenvironment which may support the growth and proliferation of transformed cells.

• MeSH
• buněčné dělení MeSH
• buňky stromatu metabolismus   MeSH
• cytoplazma metabolismus   MeSH
• dysplazie děložního hrdla metabolismus   MeSH
• fibroblasty metabolismus   MeSH
• imunohistochemie MeSH
• invazivní růst nádoru MeSH
• karcinom in situ metabolismus   MeSH
• keratinocyty metabolismus   MeSH
• lidé MeSH
• nádory děložního čípku metabolismus   MeSH
• protoonkogen Mas MeSH
• protoonkogenní proteiny c-myc fyziologie   MeSH
• spinocelulární karcinom metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• MAS1 protein, human MeSH Prohlížeč
• MYC protein, human MeSH Prohlížeč
• protoonkogen Mas MeSH
• protoonkogenní proteiny c-myc MeSH

abl and bcr genes play an important role in the diagnostics of chronic myelogenous leukemia (CML). The translocation of these genes results in an abnormal chromosome 22 called the Philadelphia chromosome (Ph). The chimeric bcr-abl gene is a fundamental phenomenon in the pathogenesis of CML. Malignant transformation of hematopoietic cells is also accompanied by the c-myc gene changes (translocation, amplification). Nuclear topology of the abl, bcr and c-myc genes was determined in differentiated as well as in irradiated HL-60 cells using dual-colour fluorescence in situ hybridisation and image analysis by means of a high resolution cytometer. After the induction of the granulocytic differentiation of HL-60 cells with all trans retinoic acid (ATRA) or dimethylsulfoxide (DMSO), the abl and bcr homologous genes were repositioned closer to the nuclear periphery and the average distances between homologous abl-abl and bcr-bcr genes as well as between heterologous abl-bcr genes were elongated as compared with untreated human leukemic promyelocytic HL-60 cells. Elongated gene-to-gene and centre-to-gene distances were also found for the c-myc gene during granulocytic differentiation. In the case of the monocytic maturation of HL-60 cells treated with phorbol esters (PMA), the abl and bcr homologous genes were repositioned closer to each other and closer to the nuclear centre. The position of the c-myc gene did not change significantly after the PMA stimulus. The proximity of the abl and bcr genes was also found after gamma irradiation using 60Co (5 Gy). Immediately after the gamma irradiation c-myc was repositioned closer to the nuclear centre, but 24 h after radiation exposure the c-myc position returned back to the pretreatment level. The c-myc gene topology after gamma irradiation (when the cells are blocked in G2 phase) was different from that detected in the G2 sorted control population. We suggest that changes in the abl, bcr and c-myc topology in the case of gamma irradiation are not the effects of the cell cycle. It is possible, that differences in the cell cycle of hematopoietic cells after the gamma irradiation and concurrent proximity of the abl, bcr and c-myc genes could be important from the point of view of contingent gene translocations, that are responsible for malignant transformation of cells.

• MeSH
• buněčná diferenciace genetika   MeSH
• buněčné jádro patologie   účinky záření   MeSH
• buněčný cyklus genetika   MeSH
• chronická myeloidní leukemie genetika   patologie   radioterapie   MeSH
• geny abl * MeSH
• geny myc * MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• onkogenní proteiny genetika   MeSH
• protoonkogenní proteiny c-bcr MeSH
• protoonkogenní proteiny * MeSH
• regulace genové exprese u nádorů účinky záření   MeSH
• tyrosinkinasy * MeSH
• záření gama MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• BCR protein, human MeSH Prohlížeč
• onkogenní proteiny MeSH
• protoonkogenní proteiny c-bcr MeSH
• protoonkogenní proteiny * MeSH
• tyrosinkinasy * 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
• Názvy látek
• aluminum phthalocyanine disulfonate MeSH Prohlížeč
• antioxidancia MeSH
• fotosenzibilizující látky MeSH
• indoly MeSH
• organokovové sloučeniny MeSH
• porfyriny MeSH
• protoonkogenní proteiny c-fos MeSH
• protoonkogenní proteiny c-myc MeSH
• reaktivní formy kyslíku MeSH
• tetra(4-N-methylpyridyl)porphine MeSH Prohlížeč