c-MYC: more than just a matter of life and death

Pelengaris, Stella; Khan, Michael; Evan, Gérard I.

doi:10.1038/nrc904

Cited by 1,047 publications

(954 citation statements)

References 120 publications

Supporting

Mentioning

917

Contrasting

Unclassified

Order By: Relevance

“…In Burkitt lymphoma, MYC overexpression is secondary to the translocation of heavy or light immunoglobulin chains genes at a distance of 100-150 kb upstream (Joos et al, 1992) or 300 kb downstream (Henglein et al, 1989;Zeidler et al, 1994) of MYC. MYC activation was also observed in invasive carcinomas that develop in various organs such as breast, prostate, stomach or colon (Pelengaris et al, 2002). This activation, which is generally related to a moderate level of amplification, is often found in poorly differentiated tumors (Nesbit et al, 1999).…”

Section: Discussionmentioning

confidence: 96%

“…In cooperation with E6 in HPV-infected keratinocytes, MYC may also activate the telomerase reverse transcription promoter (Veldman et al, 2003). Recent data have underlined the important role of MYC in the differentiation of skin epithelium (Pelengaris et al, 2002;Alonso and Fuchs, 2003). Through the depletion of integrin b (Waikel et al, 2001), MYC was found to act selectively on epidermal stem cells (Gandarillas and Watt, 1997), driving them into the transit amplification compartment and stimulating differentiation into interfollicular epidermis and sebocytes (Frye et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

MYC activation associated with the integration of HPV DNA at the MYC locus in genital tumors

et al. 2006

View full text Add to dashboard Cite

To determine whether integration of human papillomavirus (HPV) DNA sequences could lead to the deregulation of genes implied in oncogenesis, we analysed the HPV integration sites in a series of nine cell lines derived from invasive genital carcinomas. Using in situ hybridization, HPV16 or 18 sequences were found at chromosome band 8q24, the localization of MYC, in IC1, IC2, IC3, IC6 and CAC-1 cells and at other sites in IC4, IC5, IC7 and IC8 cells. We then localized viral sequences at the molecular level and searched for alterations of MYC structure and expression in these cells. MYC genomic status and viral integration sites were also analysed in primary tumors from which IC1, IC2, IC3 and IC6 cells were derived. In IC1, IC2 and CAC-1 cells, HPV DNA was located within 58 kb of MYC, downstream, upstream, or within MYC. In IC3 and IC6 cells, HPV DNA was located 400-500 kb upstream of MYC. Amplification studies showed that, in IC1, IC2 and IC3, viral and MYC sequences were coamplified in an amplicon between less than 50 and 800 kb in size. MYC amplification was also observed in primary tumors, indicating that this genetic alteration, together with viral insertion at the MYC locus, had already taken place in vivo. MYC was not amplified in the other cell lines. MYC mRNA and protein overexpression was observed in the five cell lines in which the HPV DNA was inserted close to the MYC locus, but in none of the lines where the insertion had occurred at other sites. MYC activation, triggered by the insertion of HPV DNA sequences, can be an important genetic event in cervical oncogenesis.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

MYC activation associated with the integration of HPV DNA at the MYC locus in genital tumors

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Moreover, aberrant AID expression was capable of triggering accumulation of nucleotide alterations in the c-myc gene in cultured hepatoma-derived cells in vitro. It has been demonstrated that deregulation of c-myc has been implicated in the etiology of a wide variety of human cancers (Pelengaris et al, 2002). The deregulating mutations impact either on the c-myc gene itself or on upstream regulatory sequences, and point mutations or gene amplification of c-myc was reported in human HCC (Feitelson, 2006).…”

Section: Expression Of Aid In Human Hepatocytes Via Nf-jb Y Endo Et Almentioning

confidence: 99%

Expression of activation-induced cytidine deaminase in human hepatocytes via NF-κB signaling

et al. 2007

View full text Add to dashboard Cite

Activation-induced cytidine deaminase (AID) is involved in somatic DNA alterations of the immunoglobulin gene for amplification of immune diversity. The fact that constitutive expression of AID in mice causes tumors in various organs, including lymphoid tissues and lungs, suggests the important role of the aberrant editing activity of AID on various tumor-related genes for carcinogenesis. AID expression, however, is restricted to activated B cells under physiological conditions. We demonstrate here that ectopic AID expression is induced in response to tumor necrosis factor-a stimulation in cultured human hepatocytes. The proinflammatory cytokine-mediated expression of AID is achieved by IjB kinase-dependent nuclear factor (NF)-jB signaling pathways. Hepatitis C virus, one of the leading causes of hepatocellular carcinoma (HCC), enhanced AID expression via NF-jB activation through expression of viral core protein. The aberrant expression of AID in hepatoma-derived cells resulted in accumulation of genetic alterations in the c-myc and pim1 genes, suggesting that inappropriate expression of AID acts as a DNA mutator that enhances the genetic susceptibility to mutagenesis in human hepatocytes. Our current findings indicate that the inappropriate expression of AID is induced by proinflammatory cytokine stimulation and may provide the link between hepatic inflammation and the development of HCC.

show abstract

“…Dysregulation of c-myc induces cellular transformation in vitro and tumorigenesis in vivo (Pelengaris et al, 2002). In general, low levels of c-myc mRNA and protein are expressed in normally proliferating cells.…”

Section: Introductionmentioning

confidence: 99%

Far upstream element-binding protein-1, a novel caspase substrate, acts as a cross-talker between apoptosis and the c-myc oncogene

et al. 2009

View full text Add to dashboard Cite

Far upstream element-binding protein-1 (FBP-1) binds to an upstream element of the c-myc promoter and regulates the c-myc mRNA level. Earlier, FBP-1 was identified as a candidate substrate of caspase-7. Here, we report that FBP-1 is cleaved by executor caspases, both in vitro and during apoptosis. Cleavage occurs at the caspase consensus site (DQPD 74 ) located within the classical bipartite nuclear localization signal sequence. In cells subjected to apoptotic stimuli, the caspase-mediated cleavage of FBP-1 leads to its decreased presence in the nucleus, concomitant with the marked downregulation of c-Myc and its various target proteins. By contrast, cells transfected with a non-cleavable mutant of FBP-1 (D74A) maintain higher levels of c-Myc and are protected from apoptosis. On the basis of these results, we suggest that the oncogenic potential of c-Myc is 'switched off' after apoptosis induction as a consequence of the caspasemediated cleavage of FBP-1.

show abstract

c-MYC: more than just a matter of life and death

Cited by 1,047 publications

References 120 publications

MYC activation associated with the integration of HPV DNA at the MYC locus in genital tumors

MYC activation associated with the integration of HPV DNA at the MYC locus in genital tumors

Expression of activation-induced cytidine deaminase in human hepatocytes via NF-κB signaling

Far upstream element-binding protein-1, a novel caspase substrate, acts as a cross-talker between apoptosis and the c-myc oncogene

Contact Info

Product

Resources

About