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At least 289 records · Page 16Linked to original sources
PubMed1983

Translocation of an immunoglobulin kappa locus to a region 3' of an unrearranged c-myc oncogene enhances c-myc transcription.

We have studied somatic cell hybrids between mouse myeloma and JI Burkitt lymphoma cells carrying a t(2;8) chromosome translocation for the expression of human kappa chains. and for the presence and rearrangements of the human c-myc oncogene and kappa chain genes. Our results indicate that the c-myc oncogene is unrearranged and remains on the 8q+ chromosome of JI cells. Two rearranged C kappa genes were detected: the expressed allele on normal chromosome 2 and the excluded kappa allele that was translocated from chromosome 2 to the involved chromosome 8 (8q+). The distribution of V kappa and C kappa genes in hybrid clones retaining different human chromosomes indicated that C kappa is distal to V kappa on 2p and that the breakpoint in this Burkitt lymphoma is within the region carrying V kappa genes. High levels of transcripts of the c-myc gene were found when it resided on the 8q+ chromosome but not on the normal chromosome 8, demonstrating that translocation of a kappa locus to region distal to the c-myc oncogene enhances c-myc transcription.

Animals↗
PubMed1984

Nucleotide sequence 5' of the chicken c-myc coding region: localization of a noncoding exon that is absent from myc transcripts in most avian leukosis virus-induced lymphomas.

We have determined the nucleotide sequence of the 2.2-kilobase-pair region upstream of the chicken c-myc coding exons. Using RNA blot analysis, we have localized a noncoding exon to a region that is separated from the c-myc coding sequences by an intron of 700-800 base pairs. In most avian leukosis virus-induced lymphomas proviral integration has occurred within, or downstream of, the first exon, thus presumably displacing the regulatory sequences that normally control c-myc expression. More than 70% of the integration sites were clustered in a 250-base-pair region in the first intron, immediately preceding the coding sequences. Sequences from the upstream noncoding exon were absent from the myc transcripts in these lymphomas; RNA transcripts from the normal c-myc allele were not expressed at detectable levels.

Animals↗
PubMed1986

Amplification units containing human N-myc and c-myc genes.

The amplification units in human tumors containing amplified myc genes were examined. The amplification unit in all cases consisted of a large genomic region coamplified with the coding region of the myc genes themselves. In eight independent neuroblastomas containing N-myc amplifications, the amplification unit was estimated to be 290 to 430 kilobases. This amplification unit was highly conserved among the different neuroblastomas, with some neuroblastomas containing almost identical units. In contrast, five tumor cell lines containing c-myc amplifications exhibited amplification units that were more variable in size (90 to 300 kilobases) and sequence content; at least three different patterns of c-myc amplification units could be discerned.

Brain Neoplasms↗
PubMed1982

Isolation and biochemical characterization of partially transformation-defective mutants of avian myelocytomatosis virus strain MC29: localization of the mutation to the myc domain of the 110,000-dalton gag-myc polyprotein.

Recently, we isolated three mutants of MC29 virus which, although able to transform fibroblasts with the same efficiency as wild-type MC29, were 100-fold less efficient at transforming macrophages. In this study we found that MC29-transformed quail producer cell line Q10 was able to generate these partially transformation defective mutants at a high frequency. Using tryptic peptide mapping, we determined that the smaller gag-myc polyproteins encoded by the transformation-defective viruses had lost myc-specific tryptic peptides. This suggested that the mutations which resulted in the transformation-defective viruses being inefficient at transforming macrophages were located in the v-myc sequence and thus directly implicated v-myc and the gag-myc polyprotein in transformation by MC29.

Animals↗
PubMed1993

Myc amplification: regulation of myc function.

The myc oncogenes have been implicated in the control of cell proliferation in both normal and neoplastic cells. There is increasing evidence that Myc proteins function as transcriptional regulators of other genes apparently involved in the control of cell proliferation. The effects of Myc on both gene expression and cell growth are differentially regulated by the recently described Max and delta Max proteins that can either cooperate or compete with Myc for sequence-specific DNA binding.

Gene Amplification↗
PubMed2004

Of mice and Myc: c-Myc and mammary tumorigenesis.

The proto-oncogene c- myc is involved in regulating proliferation and apoptosis, and its deregulation via genomic and postgenomic mechanisms, contributes to the development and progression of multiple human cancers, including those of the breast. Deregulated expression of c-Myc also contributes to neoplastic transformation by altering cellular differentiation pathways and by facilitating mutagenesis through induction of genomic instability. Transgenic and gene-knockout mice are frequently utilized to resolve the mechanisms through which specific genes influence the development and progression of malignancies. In this review, we discuss how research findings obtained from various c- myc transgenic mammary tumor models help to improve our resolution of c-Myc's role both in tumorigenesis of the murine mammary gland and cancer of the human breast.

Animals↗
PubMed1992

Retroviral infection accelerates T lymphomagenesis in E mu-N-ras transgenic mice by activating c-myc or N-myc.

Transgenic mice bearing a mutant, activated N-ras oncogene directed to express within hematopoietic cells by an immunoglobulin enhancer (E mu) sporadically develop T-cell lymphomas and non-lymphoid tumors that may be of macrophage origin. To identify genes that can collaborate with N-ras in hematopoietic neoplasia, Moloney murine leukemia virus was used as an insertional mutagen. Infection of newborn E mu-N-ras mice with the virus greatly accelerated tumorigenesis, and nearly all the tumors proved to be T-cell lymphomas. Their variable surface phenotype (CD4+CD8-, CD4+CD8+ and CD4-CD8-) suggested that cells at several stages of T-cell development were susceptible to tumorigenesis. Southern blot analysis revealed that 68% of the tumors bore a proviral insert 5' to the c-myc gene, while 13% had an insert within the 3' untranslated region of the N-myc gene. Insertion was associated with elevated expression of these genes. Hence, activation of a myc gene appears to be the dominant pathway to tumorigenesis by insertional mutagenesis in lymphoid cells expressing a mutant ras gene. However, since many of the tumors were not transplantable, even the partnership of myc and ras may not suffice for full lymphoid malignancy.

Animals↗
PubMed1991

Antisense oligodeoxynucleoside methylphosphonate inhibition of mouse c-myc p65 protein expression in E mu-c-myc transgenic mice.

In transgenic mice bearing a murine immunoglobulin enhancer/c-myc fusion transgene (E mu-myc), it was found that methylphosphonates do not induce acute toxicity following intravenous administration of a 300 nmol dose. In addition, recovery of methylphosphonates from the blood plasma of treated mice indicated that the oligomers remained intact up to 3 hours, while their concentrations decreased rapidly for the first hour, then slowly decreased over the next two hours. Finally, methylphosphonate oligomers targeted against c-myc mRNA inhibited production of c-myc p65 protein in peripheral and splenic lymphocytes, relative to a scrambled sequence oligomer, 4 hours after injection of a 300 nmol dose, as indicated by immunofluorescence of fixed cells stained with an anti-c-myc antiserum.

Animals↗
PubMed1997

1,25-dihydroxyvitamin D3 regulates the expression of N-myc, c-myc, protein kinase C, and transforming growth factor-beta2 in neuroblastoma cells.

1alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) alters the proliferation of neuroblastoma cells in culture in part via a nerve growth factor (NGF)-mediated pathway. This suggests that factors other than NGF also play a role in the growth arrest induced by 1,25(OH)2D3. To more fully characterize the effect of 1,25(OH)2D3 on neuroblastoma cells, we treated the cells with 10(-8) M 1,25(OH)2D3 and examined the cells for changes in the expression of N-myc, c-myc, transforming growth factor-beta2 (TGF-beta2), and protein kinase C (PKC) activity. Our results show that 1,25(OH)2D3 causes a decrease in the expression of N-myc and c-myc, as well as a two-fold increase in total PKC activity and a dose-dependent increase in TGF-beta2 expression. These results show that 1,25(OH)2D3 regulates the expression of growth-regulatory factors other than NGF in neuroblastoma cells and that 1,25(OH)2D3 influences the growth of neural cells via multiple growth regulatory pathways.

Animals↗
PubMed1988

Localization in situ of c-myc mRNA and c-myc protein in adult mouse testis.

It has been suggested that c-myc, one of the proto-oncogenes, plays a role in normal somatic cell proliferation and differentiation. To define whether c-myc is only expressed during somatic cell division or is also expressed during meiotic cell division, the production of c-myc mRNA and protein were investigated in the mouse testis by using in situ hybridization with non-radioactive DNA probes and enzyme immunohistochemistry respectively. For in situ hybridization, T-T dimerized DNA probes were used and DNAs hybridized in situ were detected immunohistochemically using specific antibody against T-T dimer. The results indicate that c-myc mRNA and protein are expressed in a cell-cycle-dependent manner only in spermatogonia and not in spermatocytes and spermatids.

Animals↗
PubMed1989

Elevation of c-myc transcript level in human liver during surgical resection of hepatocellular carcinoma: possible cause for underestimation of c-myc gene activation in the tumor.

It has been a matter of controversy as to whether c-myc gene expression is activated in human hepatocellular carcinoma (HCC). We observed that the c-myc mRNA level in HCC was similar to that of the adjacent non-cancerous portion, as determined in freshly obtained specimens after a partial liver resection. However, the c-myc transcript was at a low level in non-cancerous tissue which was biopsied prior to surgery, whereas it was still at a high level in HCC obtained without performing hepatectomy. These results suggest that the high transcript level observed in the non-cancerous tissue from the excised liver relates to liver resection itself, and that the c-myc gene expression is enhanced in the HCC.

Blotting, Northern↗
PubMed2000

ENO1 gene product binds to the c-myc promoter and acts as a transcriptional repressor: relationship with Myc promoter-binding protein 1 (MBP-1).

The Myc promoter-binding protein-1 (MBP-1) is a 37-38 kDa protein that binds to the c-myc P2 promoter and negatively regulates transcription of the protooncogene. MBP-1 cDNA shares 97% similarity with the cDNA encoding the glycolytic enzyme alpha-enolase and both genes have been mapped to the same region of human chromosome 1, suggesting the hypothesis that the two proteins might be encoded by the same gene. We show here data indicating that a 37 kDa protein is alternatively translated from the full-length alpha-enolase mRNA. This shorter form of alpha-enolase is able to bind the MBP-1 consensus sequence and to downregulate expression of a luciferase reporter gene under the control of the c-myc P2 promoter. Furthermore, using alpha-enolase/green fluorescent protein chimeras in transfection experiments we show that, while the 48 kDa alpha-enolase mainly has a cytoplasmic localization, the 37 kDa alpha-enolase is preferentially localized in the cell nuclei. The finding that a transcriptional repressor of the c-myc oncogene is an alternatively translated product of the ENO1 gene, which maps to a region of human chromosome 1 frequently deleted in human cancers, makes ENO1 a potential candidate for tumor suppressor.

Alternative Splicing↗
PubMed2002

Unsaturated fatty acids bind Myc-Max transcription factor and inhibit Myc-Max-DNA complex formation.

Oncoprotein Myc, hetero-dimerized with Max through a b/HLH/Zip region, is a transcription factor that governs important cellular processes such as cell cycle entry, proliferation and differentiation. We found that linoleic acid, isolated from Pollen Typhae, and other unsaturated fatty acids have strong inhibitory effects on the binding of Myc-Max heterodimer to an E-box DNA site (CA(C/T)GTG). The interaction of a fatty acid with a protein dimer, not with DNA, is assumed to block the entire Myc-Max-DNA complex formation. Unsaturated fatty acids also showed cytotoxicity against a SNU16 human stomach cancer cell line and conjugated linoleic acid suppressed mRNA expression of several myc-target genes; ornithine decarboxylase, p53, cdc25a in the SNU16 cells.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1992

Expression of c-myc and c-fos in rat skeletal muscle. Evidence for increased levels of c-myc mRNA during hypertrophy.

The levels of c-myc and c-fos mRNA were investigated in rat skeletal muscle by Northern hybridization. During post-natal development in the rat, c-myc mRNA levels were similar at birth and at 7 and 21 days of age, but then declined at 90 days and were barely detectable at 1 year. c-fos mRNA levels followed this pattern of expression until 90 days, but showed a large increase at 1 year. Hypertrophy of soleus and plantaris muscles was induced either by severance of the tendon to the synergistic gastrocnemius (tenotomy) or by administration of the beta-adrenoceptor agonist clenbuterol. In both cases hypertrophy was associated with a rapid increase in c-myc mRNA levels. Following tenotomy the increase was both greater (8-fold) and more rapid (3 h) in soleus than in plantaris (2-3 fold, 12 h). Similar effects were observed during clenbuterol administration. Neither treatment caused any alteration in c-fos mRNA levels in the plantaris muscle. The results show that increased c-myc mRNA levels are an early event in the response of skeletal muscle to hypertrophic stimuli; it is argued that this occurs within the differentiated skeletal muscle fibres.

Aging↗
PubMed2002

Physical interaction of p73 with c-Myc and MM1, a c-Myc-binding protein, and modulation of the p73 function.

p73 shares high sequence homology with the tumor suppressor p53. Like p53, ectopic overexpression of p73 induces cell cycle arrest and/or apoptosis, and these biological activities are linked to its sequence-specific transactivation function. The COOH-terminal region of p73 is unique and has a function to modulate DNA-binding ability and transactivation activity. To identify and characterize cellular proteins that interact with the COOH-terminal region of p73 alpha and regulate its activity, we employed a yeast-based two-hybrid screen with a human fetal brain cDNA library. We found MM1, a nuclear c-Myc-binding protein, was associated with p73 alpha in both yeast two-hybrid and in vitro pull-down assays. In mammalian cells, MM1 co-immunoprecipitated with p73 alpha, whereas p73 beta and tumor suppressor p53 did not interact with MM1. Overexpression of MM1 in p53-deficient osteosarcoma SAOS-2 cells enhanced the p73 alpha-dependent transcription from the p53/p73-responsive Bax and PG13 promoters, whereas p73 beta- and p53-mediated transcriptional activation was unaffected in the presence of MM1. MM1 also stimulated the p73 alpha-mediated growth suppression in SAOS-2 cells. More importantly, we found that c-Myc was physically associated with p73 alpha and significantly impaired the transcriptional activity of p73 alpha on Bax and p21(waf1) promoters. Expression of MM1 strongly reduced the c-Myc-mediated inhibitory activity on p73 alpha. These results suggest that MM1 may act as a molecular partner for p73 to prevent the c-Myc-mediated inhibitory effect on its activity.

Base Sequence↗
PubMed1987

Elevated myc expression and c-myc amplification in spontaneously occurring B lymphoid cell lines.

Recently, a minor subpopulation of murine B lymphocytes, Ly-1+ B cells, has been distinguished by its unique ontogeny, tissue distribution, and prominence in certain autoimmune and neoplastic B cell diseases. We have previously described a simple murine spleen culture system that results in the spontaneous and exclusive outgrowth of long-term Ly-1+ B cell lines (B Ly-1 cells). Here, we report that the immortal growth property of B Ly-1 cells correlates with a 10-45-fold elevation of steady-state myc RNA and 2-10-fold amplification of the c-myc locus. While c-myc amplification has been observed in malignant cell lines derived from several tissues of origin, its occurrence in lymphoid cells has not been previously reported. The consistent c-myc amplification in B Ly-1 cells may reflect a unique state of this locus in the Ly-1+ B lymphocyte lineage, and contribute to the spontaneous immortalization of this B cell population in vitro, and its apparent predilection for malignant transformation in vivo.

Animals↗
PubMed1990

Excision of N-myc from chromosome 2 in human neuroblastoma cells containing amplified N-myc sequences.

Amplification of one of three growth-stimulating myc genes is a common method by which many tumor types gain a proliferative advantage. In metastatic human neuroblastoma, the amplification of the N-myc locus, located on chromosome 2, is a dominant feature of this usually fatal pediatric cancer. Of the many models proposed to explain this amplification, all incorporate as the initial step either disproportionate overreplication of the chromosomal site or recombination across a loop structure. The original locus is retained within the chromosome in the overreplication models but is excised in the recombination models. To test these models, we have used somatic cell hybrids to separate and analyze the chromosomes 2 from a neuroblastoma cell line containing in vivo amplified N-myc. Our results demonstrate that N-myc is excised from one of the chromosomes, suggesting that deletion is a requisite part of gene amplification in a naturally occurring system.

Animals↗
PubMed2006

Regulation of the Arf tumor suppressor in Emicro-Myc transgenic mice: longitudinal study of Myc-induced lymphomagenesis.

Lymphomagenesis in Emu-Myc mice is opposed by the Arf tumor suppressor, whose inactivation compromises p53 function and accelerates disease. Finding nascent Emu-Myc-induced tumors in which p19Arf causes cell-cycle arrest or apoptosis is problematic, since such cells will be eliminated until Arf or p53 function is lost. Knock-in mice expressing a green fluorescent protein (GFP) in lieu of Arf coding sequences allow analysis of Arfpromoter regulation uncoupled from p19Arf action. Prior to frank lymphoma development, unexpectedly low levels of Emu-Myc-induced p19Arf or GFP were expressed. However, as lymphomas arose in Arf+/GFP heterozygotes, additional oncogenic events synergized with Emu-Myc to further induce the functionally null Arf-Gfp allele. Concomitant up-regulation of p19Arf was not observed; instead, the wild-type allele was inactivated. We infer that very low levels of Arf are tumor suppressive, and that further induction provides the selective pressure for the emergence of tumors that have inactivated the gene.

Animals↗