Pleiotropic derepression of developmentally regulated cellular and viral genes by c-myc proto-oncogene products in undifferentiated embryonal carcinoma cells

Onclercq, Rosine; Lavenu, A.; Crémisi, C

doi:10.1093/nar/17.2.735

Cited by 18 publications

(18 citation statements)

References 42 publications

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“…Similar results were also reported for the cytokeratin murine endoA and endoB and early adenovirus E4 promoters (Onclercq et al, 1988(Onclercq et al, , 1989.…”

Section: Discussionsupporting

confidence: 88%

“…In contrast, the deleted-exon1 or mutated c-myc vectors expressing only one of the other c-Myc protein, not only lost this activating property, but became strong repressors of Ecadherin expression. These results imply that both cMyc proteins are required to positively regulate the Ecadherin promoter, as previously suggested for the Endo A gene coding for a cytokeratin (Onclercq et al, 1989), and that the ratio between the two c-Myc proteins, which is regulated at the translational level, is presumably very important since activation by wild type c-myc is inhibited in a dose-dependent manner by overexpression of one or other of the c-Myc proteins alone. Cell density, Max levels, cell type and cell state (undierentiated, dierentiated or tumoral) might be important criteria for determining this ratio.…”

Section: Discussionsupporting

confidence: 79%

“…cmyc would repress or activate the same gene depending on whether the cell is dierentiated, undierentiated or tumoral (see also CreÂ misi, 1989). The ratio of the two c-Myc proteins might be dierent in these dierent situations.…”

Section: Discussionmentioning

confidence: 99%

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Opposite transcriptional activity between the wild type c-myc gene coding for c-Myc1 and c-Myc2 proteins and c-Myc1 and c-Myc2 separately

Batsché

Crémisi

1999

Oncogene

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E-cadherin expression was previously shown to be activated by RB and c-myc speci®cally in epithelial cells, through interaction with the AP-2 transcription factor. Here we show that only a wild type c-myc gene, coding for the two c-Myc proteins c-Myc2 and c-Myc1, was able to transactivate the E-cadherin promoter, in contrast to c-Myc2 or c-Myc1 alone which strongly repressed E-cadherin in both epithelial cells and ®broblasts. In addition, overexpression of c-myc2 or cmyc1 inhibited c-myc and RB-mediated activation in a dose-dependent manner, suggesting that the ratio of the two c-Myc proteins is essential for transactivation. We also showed by using several mutants of the E-cadherin promoter, that the AP-2 binding sites were the main target of c-myc2-and c-myc1-mediated repression. AP-2-mediated inhibition was cell-type speci®c, as was the activation. Nevertheless, when high amounts of c-myc2 and c-myc1 were used, a second c-myc-mediated repression was observed, possibly mediated by the Inr sequence of the E-cadherin promoter. However, this repression was independent of cell type. Our results suggest a new way to regulate c-myc transcriptional activity by interfering with the ratio of the two c-myc proteins, which has already been found to be disrupted in vivo in several tumor types.

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“…Similar results were also reported for the cytokeratin murine endoA and endoB and early adenovirus E4 promoters (Onclercq et al, 1988(Onclercq et al, , 1989.…”

Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 79%

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Opposite transcriptional activity between the wild type c-myc gene coding for c-Myc1 and c-Myc2 proteins and c-Myc1 and c-Myc2 separately

Batsché

Crémisi

1999

Oncogene

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“…Labeled probes (0.5 Ag) specific to either the N-myc or c-myc gene were pooled, respectively, with HPV45 and HPV18 probes or HPV16. The c-myc probe spans 12 kb (22), corresponding to the gene (6 kb) and 5V regulatory sequences. A plasmid containing the cloned N-myc gene was used (6.5 kb).…”

Section: Methodsmentioning

confidence: 99%

Genomic Organization of Amplified MYC Genes Suggests Distinct Mechanisms of Amplification in Tumorigenesis

Herrick¹,

Conti²,

Teissier

et al. 2005

Cancer Research

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Integration of the human papillomavirus (HPV) genome into the host genome is associated with the disruption of the HPV E2 gene and with amplification and rearrangement of the viral and flanking cellular sequences. Molecular characterization of the genomic structures of coamplified HPV sequences and oncogenes provides essential information concerning the mechanisms of amplification and their roles in carcinogenesis. Using fluorescent hybridization on stretched DNA molecules in two cervical cancer-derived cell lines, we have elucidated the genomic structures of amplified regions containing HPV/myc genes over several hundreds of kilobases. Direct visualization of hybridization signals on individual DNA molecules suggests that overreplication and breakagefusion-bridge-type mechanisms are involved in the genomic instability associated with HPV cervical cancers. Further analysis from two other genital cancer-derived cell lines reveals a recurrent motif of amplification, probably generated by a common mechanism involving overreplication upon viral integration. Interestingly, different amplification patterns seem to be correlated with the disease outcome, thus providing new insights into HPV-related cancer development and tumor progression. (Cancer Res 2005; 65(4): 1174-9)

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“…Although many reports suggest that the cnzyc protein is directly or indirectly involved in transcription and/or DNA replication, there is still no strong consensus about its molecular functions (for reviews see [l-4]). As for its transcriptional functions, it was reported that c-nlyc protein activated the heat shock 70(HSP70) promoter and repressed the metallothionein promoter [5,6], and that the adenovirus E4 promoter could be transactivated by the c-myc protein through the same promoter region required for Ela activation [7]. Recently, using a c-myc-steroid receptor fusion protein that permits hormone-dependent myc activity [S], a myc-inducible transcript has been identified which is related to the cz-prothymosin gene [S].…”

Section: Introductionmentioning

confidence: 99%

Activation of c‐myc promoter by c‐myc protein in serum starved cells

et al. 1991

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The function of the c-myc protein, the product of a proto oncogene, is not clearly understood although many reports, including ours, suggest that the c-myc protein plays several roles in the regulation of transcription and DNA replication. Here we examined the effects of c-myc protein on transcription from the c-myc promoter, and by inference its role in auto-regulation, after introducing into cultured cells a c-myc expression vector and a CAT reporter gene linked to the promoter and upstream region of the human c-myc gene. To minimize the effects of the endogenous c-myc protein on the exogenously added CAT reporter gene, the transfected cells were treated under serum-free conditions. The results show that CAT expression from the myc promoter increased in a dose-dependent manner Efter addition of the c-myc expression vector, and that it also required the presence of a c-myc binding sequence previously identified 2 kb upstream from c-myc's first exon.Moreover, the domains of the c-myc protein important for transactivation were determined by use of various deletions mutants of c-myc cDNA. The results showed that the N-terminal portion in the c-myc protein was necessary for transactivation beside the C-terminal portion containing basic region, helix-loop-helix, and leucine zipper.

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Pleiotropic derepression of developmentally regulated cellular and viral genes by c-myc proto-oncogene products in undifferentiated embryonal carcinoma cells

Cited by 18 publications

References 42 publications

Opposite transcriptional activity between the wild type c-myc gene coding for c-Myc1 and c-Myc2 proteins and c-Myc1 and c-Myc2 separately

Opposite transcriptional activity between the wild type c-myc gene coding for c-Myc1 and c-Myc2 proteins and c-Myc1 and c-Myc2 separately

Genomic Organization of Amplified MYC Genes Suggests Distinct Mechanisms of Amplification in Tumorigenesis

Activation of c‐myc promoter by c‐myc protein in serum starved cells

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