Telomeres, telomerase, and myc. An update

Cerni, Christa

doi:10.1016/s1383-5742(99)00091-5

Cited by 127 publications

(85 citation statements)

References 122 publications

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“…Telomerase expression is associated with the progression of cancer and endogenous upregulation of hTERT gene expression by the protooncogene cMyc [6]. Thus, the possibility of malignant transformation arises when somatic cells are engineered to continually express telomerase for use in cell and gene therapy.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cell and Nucleus Pulposus Cell Coculture Modulates Cell Profile

Niu

Yuan

Lin

et al. 2008

Clin Orthop Relat Res

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Spontaneous cell fusion can occur in cocultured stem cells. We examined whether telomerase activity change and cell fusion occurred in mesenchymal stem cell (MSC) and nucleus pulposus cell (NPC) coculture. MSCs and NPCs were labeled with PKH26 and PKH67 dyes and cocultured at a 50:50 ratio. An equal number of MSCs or NPCs were used as the control. After 14 days, cells were evaluated by cell growth, telomerase activity, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and histologic observation. Cell fusion was confirmed by microscopic observation and fluorescence-activated cell sorter (FACS) analysis. The results suggested cell growth rate and telomerase activity were higher in cocultured cells than in NPCs cultured alone. The mRNA expression levels of the Type II collagen and aggrecan were elevated in cocultured cells. Immunohistochemical analysis revealed positive staining for Type II collagen and keratan sulfate in NPCs cultured alone and in a proportion of cocultured cells. Histologic observation revealed binucleated cocultured cells expressed both PKH dyes in the same location and slide focus. The FACS analysis revealed 42% of cocultured cells were doublestained. Cocultured cells partially maintained the NPC phenotype. The partially maintained phenotype of the NPCs may be attributable to spontaneous cell fusion in association with increased telomerase activity.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cell and Nucleus Pulposus Cell Coculture Modulates Cell Profile

Niu

Yuan

Lin

et al. 2008

Clin Orthop Relat Res

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“…Among the increasing number of Myc-regulated genes, the recently discovered E-box sequences in the promoter of the gene encoding the catalytic component of human telomerase, hTERT (Wu et al, 1999;Greenberg et al, 1999), are of special interest since re-activation of telomerase is an obligatory ®nding in many human malignancies (for review see Shay and Bacchetti, 1997). It is an attractive hypothesis that overexpressed Myc promotes cellular immortalization at least in part through reactivation of hTERT (for review see Cerni, 2000). Indeed, myc genes are deregulated in a large number of human tumors and a ect both the development and progression of hyperproliferations (see DePinho et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Repression of in vivo growth of Myc/Ras transformed tumor cells by Mad1

et al. 2002

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The Myc/Max/Mad network of transcriptional regulatory proteins plays an essential role in cell proliferation, growth, apoptosis, and di erentiation. Whereas Myc proteins a ect cell cycle progression positively, Mad proteins are negative regulators of cell proliferation. It has been shown in several in vitro systems that Mad proteins antagonize c-Myc functions. In this report we describe the inhibition of tumor cell outgrowth in vivo by Mad1 expression. Transformed cell lines were generated by co-transfection of c-myc, c-H-ras, and a chimeric mad1ER construct into primary rat embryo cells (MRMad1ER cells). Activation of Mad1 by 4-Hydroxy-Tamoxifen (OHT) resulted in abrogation of telomerase activity, reduced cloning e ciency, and decreased proportion of cells in S phase. Injection of MRMad1ER cells into syngenic rats induced aggressively growing tumors after a short latency period. This tumor growth was inhibited by OHT-treatment of animals, with the extent of inhibition correlating with the amount of OHT injected. No e ect of OHT on tumor growth was observed with similarly transformed Myc/Ras cell lines which did not express Mad1ER. These data demonstrate that Mad1 is able to suppress Myc/Ras-mediated transformation under in vivo conditions.

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“…A number of recent researches indicate that c-myc activation is associated with tumor initiation and progression (Wu et al, 1999). hTERT is a downstream target of c-myc which binds to E-box and promotes expression of the hTERT genes (Henriksson & Luscher, 1996;Cerni, 2000). Therefore, c-myc and hTERT have been considered as the key factors on the anti-telomerase strategy for cancer therapy (Ward & Thompson, 2012;.…”

Section: Discussionmentioning

confidence: 99%