An active chromatin structure acquired by translocated c-myc genes.

Kakkis, E; Prehn, J; Calame, K

doi:10.1128/mcb.6.4.1357

Cited by 14 publications

(13 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result contrasts with findings for plasmacytomas, in which the region surrounding the unrearranged c-mvnc gene is insensitive to DNase I (30) and is therefore considered to be in a condensed configuration. To ensure that the general degree of DNase digestion was the same between the monocyte tumors and P388D1, the blots in Fig.…”

Section: Resultscontrasting

confidence: 54%

Germ line c-myc is not down-regulated by loss or exclusion of activating factors in myc-induced macrophage tumors.

Schuler¹,

Steele²,

Cole³

1989

Mol. Cell. Biol.

View full text Add to dashboard Cite

As in tumors with c-myc chromosomal translocations, c-myc retrovirus-induced monocyte tumors constitutively express an activated form of c-myc (the proviral gene), whereas the normal endogenous c-myc genes are transcriptionally silent. Treatment of these retrovirus-induced tumor cells with a number of bioactive chemicals and growth factors that are known to induce c-myc expression in cells of the monocyte lineage failed to induce the endogenous c-myc gene. In contrast, the same treatments induced the c-fos gene in both tumors and a control macrophage line. To investigate c-myc suppression further, a normal copy of the human c-myc gene was introduced into tumor and control cell lines by using a retrovirus with self-inactivating long terminal repeats. This transduced normal gene was expressed at equivalent levels in all cells, regardless of the state of endogenous c-myc gene expression, and was strongly induced by agents that induce the normal gene in the control cells. These results indicate that the signal transduction pathways that normally activate the c-myc gene are functional in myc-induced tumor cells and suggest that endogenous c-myc is actively suppressed. An examination of the c-myc locus itself showed that the lack of transcriptional activity correlated with the absence of several prominent DNase I-hypersensitive sites in the 5'-flanking region of the gene but without loss of general DNase sensitivity. Furthermore, analysis of 22 methylation-sensitive restriction enzyme sites in the 5'-flanking region, first exon, and first intron indicated that the silent c-myc genes remained in the same unmethylated state as did actively expressed genes. Thus, c-myc suppression does not appear to result from the most frequently described mechanisms of gene inactivation.

show abstract

Section: Resultscontrasting

confidence: 54%

Germ line c-myc is not down-regulated by loss or exclusion of activating factors in myc-induced macrophage tumors.

Schuler¹,

Steele²,

Cole³

1989

Mol. Cell. Biol.

View full text Add to dashboard Cite

show abstract

“…13 and unpublished work); thus c-myc repression occurs at the transcriptional level. This is consistent with the inactive chromatin structure of the normal c-myc gene in plasmacytomas as demonstrated by DNase I sensitivity (14). The expressed c-myc gene in the pre-B-cell line 18-81 has relatively open chromatin structure; it is more sensitive to DNase I than either the active immunoglobulin heavy-chain enhancer region or the inactive immunoglobulin a-heavy-chain constant region (E.K., unpublished results).…”

supporting

confidence: 74%

“…2; reaction mixtures with competitor contained 1 ug less poly(dI-dC)poly(dI-dC) and were incubated 5-10 min before labeled probe was added. Nonspecific competitor in a, b, c, e, f, g, and h is Hpa II-cut pBR322; nonspecific competitors in d are XbSs, a 900-bp Xba I-Sst I fragment that covers the second coding exon of c-myc, and XbXb, a 1.9-kb EcoRI-Xba I fragment from the 5' region of the murine immunoglobulin a constant gene segment (14).…”

mentioning

confidence: 99%

A plasmacytoma-specific factor binds the c-myc promoter region.

Kakkis

Calame²

1987

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

We used an electrophoretic mobility-shift assay to study proteins that bind to sequences in the 5' flanking region of the murine c-myc gene. By comparing the DNAprotein complexes formed with extracts from cells representing earlier stages of B-cell development with those from plasmacytomas, we identified a plasmacytoma-specific protein that binds to a region within the c-myc promoter. Five other regions of this promoter show extensive sequence-specific binding, but the binding is not clearly B-cell stage-specific. Methylationinterference and o-phenanthroline/copper-protection experiments identified a single plasmacytoma-specific protein binding site 290 base pairs 5' of the transcription start site

show abstract

“…Its permanent activation and/ or amplification would eliminate the need for growth factors such as PDGF and the Caz+/PIP 2 breakdown signal they generate, sensitize the cells to progression factors, and 'immortalize' them by locking them into the proliferative mode, a necessary first step in neoplastic development [59,399,418]. Indeed, mouse plasmacytoma cells, Burkitts lymphoma cells, promyelocytic leukemia ceils and human oat cell bronchial carcinomas have permanently activated their c-myc proto-oncogenes by translocating them from their normal chromosomal loci to active sites on other chromosomes and the control of stronger promoters or by amplifying them [54, 59,398,427,428]. If the 'immortalized' cells should then undergo a second change which causes them to start making an 'activated' mutant RAS protein, or permanently activate the RAS product's target CDC gene(s) that starts the chromosome replication/mitosis program, they will be completely disengaged from the normal control system and fully neoplastic [411].…”

Section: Ca 2+ Signals Oncogenes and Cancermentioning

confidence: 99%

Calcium, cyclic AMP and protein kinase C ? partners in mitogenesis

Whitfield¹,

Durkin²,

Franks³

et al. 1987

Cancer Metast Rev

View full text Add to dashboard Cite

Evidence is steadily mounting that the proto-oncogenes, whose products organize and start the programs that drive normal eukaryotic cells through their chromosome replication/mitosis cycles, are transiently stimulated by sequential signals from a multi-purpose, receptor-operated mechanism (consisting of internal surges of Ca2+ and bursts of protein kinase C activity resulting from phosphatidylinositol 4,5-bisphosphate breakdown and the opening of membrane Ca2+ channels induced by receptor-associated tyrosine-protein kinase activity) and bursts of cyclic AMP-dependent kinase activity. The bypassing or subversion of the receptor-operated Ca2+/phospholipid breakdown/protein kinase C signalling mechanism is probably the basis of the freeing of cell proliferation from external controls that characterizes all neoplastic transformations.

show abstract

An active chromatin structure acquired by translocated c-myc genes.

Cited by 14 publications

References 24 publications

Germ line c-myc is not down-regulated by loss or exclusion of activating factors in myc-induced macrophage tumors.

Germ line c-myc is not down-regulated by loss or exclusion of activating factors in myc-induced macrophage tumors.

A plasmacytoma-specific factor binds the c-myc promoter region.

Calcium, cyclic AMP and protein kinase C ? partners in mitogenesis

Contact Info

Product

Resources

About