Genomic instability in MycER-activated Rat1A-MycER cells

Mai, Sabine; Fluri, Monika; Siwarski, D; Hüppi, Konrad

doi:10.1007/bf02257272

Cited by 81 publications

(53 citation statements)

References 25 publications

(37 reference statements)

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“…Regardless of the cellular location of c-Myc, it seems that there is a higher percentage of breast cancer cases showing aberrant c-Myc protein levels than the percentage with the gene amplification. This implies that, in many cases, altered expression or altered stability of the mRNA or protein may be the mechanism for the increased levels of c-Myc, consistent with the initial report that c-Myc overexpression precedes its gene amplification and plays a role in amplification of multiple other genes and in other chromosomal instability events (Mai 1994, Mai et al 1996.…”

Section: The C-myc Gene In Human Breast Cancersupporting

confidence: 82%

“…Several reports have shown an association of c-myc gene amplification with a poor prognosis of breast cancer (Berns et al 1992c,d, 1996, Borg et al 1992, Roux-Dosseto et al 1992, Scorilas et al 1999, whereas many other studies do not find such a correlation (Table 1; Deming et al 2000). Reports on the prognostic value of overexpression of c-myc mRNA or protein are not only inconsistent but also conflicting (Table 1).…”

Section: Relevance Of the C-myc Gene To Breast Cancer Prognosis And Tmentioning

confidence: 99%

See 1 more Smart Citation

c-Myc in breast cancer.

Liao¹,

Dickson²

2000

Endocrine-Related Cancer

314

265

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Ever since Bishop and his co-workers discovered the c-myc gene in the late 1970s (Bishop 1982), voluminous literature has documented its central role in proliferation and malignant transformation of human and animal cells (Amati et al. 1998, Bouchard et al. 1998, Dang et al. 1999). Most, if not all, types of human malignancy have been reported to have amplification and/or overexpression of this gene, although the frequency of these alterations varies greatly among different reports (Nesbit et al. 1999). In 1992, researchers started to realize that aberrant expression of c-myc could cause apoptosis (Evan et al. 1992, Shi et al. 1992), although the phenomenon had actually been observed much earlier (Wurm et al. 1986). Studies in recent years have further shown that the c-myc gene regulates growth, both in the sense of cell size and in the context of tissue differentiation (Gandarillas & Watt 1997, Iritani & Eisenman 1999, Johnston et al. 1999, Schmidt 1999, Schuhmacher et al. 1999). Thus, it is now known that the c-myc gene participates in most aspects of cellular function, including replication, growth, metabolism, differentiation, and apoptosis (Packham & Cleveland 1995, Hoffman & Liebermann 1998, Dang 1999, Dang et al. 1999, Elend & Eilers 1999, Prendergast 1999). How the c-Myc protein may be specifically directed to perform one, but not the others, of these functions is still obscure, despite the fact that the relevant literature has been accumulating at a fast pace in the past two decades. This review focuses on the profound roles of c-Myc in breast cancer and in the actions of the hormones that are eitologically related to breast cancer.

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Section: The C-myc Gene In Human Breast Cancersupporting

confidence: 82%

Section: Relevance Of the C-myc Gene To Breast Cancer Prognosis And Tmentioning

confidence: 99%

c-Myc in breast cancer.

Liao¹,

Dickson²

2000

Endocrine-Related Cancer

314

265

View full text Add to dashboard Cite

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“…Such illegitimate replication a ects the stability of R2 and presumably other genes in this and additional chromosomal regions, setting the stage for both intrachromosomal and extrachromosomal ampli®cation that involves R2 (Kuschak et al, 1999) and other genes (Mai, 1994;Mai et al, 1996aMai et al, , 1999. Global changes in replication initiation and timing will contribute to the dynamics of karyotypic instability (Mai et al, 1996b;Felsher and Bishop, 1999a,b) via DNA breakage, deletions, chromosomal rearrangements, and fusions. It is evident that replication-driven mechanisms act early during cMyc-dependent initiation of R2 gene ampli®cation.…”

Section: Discussionmentioning

confidence: 99%

c-Myc initiates illegitimate replication of the ribonucleotide reductase R2 gene

Kuschak

Taylor

et al. 2002

Oncogene

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The mechanisms through which the oncoprotein c-Myc initiates locus-speci®c gene ampli®cation are not understood. When analysing the initiation mechanism of cMyc-dependent ampli®cation of the mouse ribonucleotide reductase R2 (R2) gene, we observe c-Myc-dependent initiation of illegitimate DNA replication of the R2 gene. We demonstrate multiple simultaneous c-Myc-induced R2 replication forks, whereas R2 normally replicates with a single fork. In contrast, cyclin C replicates with only a single replication fork irrespective of c-Myc deregulation. In addition to de novo replication forks, cMyc also initiates bi-allelic replication of R2, abrogating its normal mono-allelic replication pattern. Moreover, several chromosomal regions also display c-Myc-induced illegitimate replication pro®les. Thus, c-Myc can act as an illegitimate replication-licensing factor that promotes de novo replication initiation and illegitimate replication timing that adversely impacts upon genomic stability. Oncogene (2002) 21, 909 ± 920.

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“…A role for c-myc as a mutator gene in B-lineage and plasma cells has yet to be demonstrated, but studies in other cell lineages strongly support such a hypothesis. [35][36][37][38] Frederic Mushinski for reading the manuscript and providing editorial assistance.…”

Section: Figurementioning

confidence: 99%

Clonal diversification of primary BALB/c plasmacytomas harboring T(12;15) chromosomal translocations

2000

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DNA sequence analysis of PCR amplified Igh/c-myc junction fragments of T(12;15) chromosome translocations and immunohistochemical determination of immunoglobulin isotype production were employed to study the clonal diversification of neoplastic translocated plasma cells that resided in peritoneal inflammatory granulomas of BALB/c mice harboring primary plasmacytomas. The diversity of plasma cells was found to take two major forms when the fine structure of the T(12;15) translocation was used as the clonotypic marker. First, mosaics of clones containing translocations that were apparently unrelated to each other were detected in nine out of 17 (53%) mice. Second, subclones derived from common T(12;15) + progenitors by either secondary deletions in translocation breakpoint regions or aberrant isotype switching near translocation breaksites were found in five of 17 (29.5%) mice. When Ig expression was utilized as the clonotypic marker, clonal mosaics were shown to occur in all mice. This was demonstrated by the finding that the prevalent IgA-or IgG-producing plasmacytoma clone was invariably accompanied by smaller clones of IgG-or IgA-expressing neoplastic plasma cells, respectively. These results provided new insights into the clonal diversification at the terminal stage of plasmacytomagenesis. In addition, they suggested that BALB/c plasmacytomas may be uniquely useful for studying clonal diversity during B cell oncogenesis, since clonal evolution can be evaluated in a pool of tumor and tumor precursor cells that is clearly defined by the T(12;15) chromosomal translocation and the production of monoclonal immunoglobulin. Leukemia (2000) 14, 909-921.

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Genomic instability in MycER-activated Rat1A-MycER cells

Cited by 81 publications

References 25 publications

c-Myc in breast cancer.

c-Myc in breast cancer.

c-Myc initiates illegitimate replication of the ribonucleotide reductase R2 gene

Clonal diversification of primary BALB/c plasmacytomas harboring T(12;15) chromosomal translocations

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