Insulin-like growth factor I expression by tumors of neuroectodermal origin with the t(11;22) chromosomal translocation. A potential autocrine growth factor.

Yee, Douglas; Favoni, Roberto E.; Lebovic, Gail S.; Lombana, F; Powell, David R.; Reynolds, C. Patrick; Rosen, Neal

doi:10.1172/jci114910

Cited by 157 publications

(119 citation statements)

References 41 publications

Supporting

Mentioning

113

Contrasting

Unclassified

Order By: Relevance

“…Most of the EWS tumors carry the t(11;22)(q24;q12) translocation resulting in expression of fused EWS/ FLI-1 protein, including the A4573 cell line used in the present study (Yee et al, 1990;Delattre et al, 1992). The suppression of EWS/FLI-1 transcription using antisense cDNA or dominant-negative constructs resulted in growth inhibition of EWS cells in vitro indicating the involvement of this chimeric oncoprotein in regulation of cell proliferation (Kovar et al, 1996).…”

Section: Inhibition Of Ets1 Expression Enhances Growth Retardation Ofmentioning

confidence: 82%

Regulation of the human poly(ADP-ribose) polymerase promoter by the ETS transcription factor

et al. 1999

View full text Add to dashboard Cite

Ewing's sarcoma (EWS) cells accumulate elevated steady-state levels of poly (ADP-ribose) polymerase (PARP) mRNA and protein. To understand the molecular mechanisms underlying PARP upregulation, we cloned and analysed the 5'-¯anking region of the PARP gene from EWS cells. Nucleotide sequence analysis demonstrated no variations in the PARP promoter region in EWS cells. The PARP promoter encompasses multiple binding motifs for the ETS transcription factor. We have also observed that there is a coordinated up-regulation of the expression of both PARP and ETS1, relative to cells of other human tumor types expressing lower levels of PARP. Transient coexpression of ETS1 in EWS cells resulted in a strong enhancement of PARP-promoter activity. The participation of ETS in the regulation of PARP gene expression was further demonstrated in EWS cells stably transfected with Ets1 antisense cDNA constructs. Antisensemediated down-regulation of endogenous ETS1 resulted in the inhibition of PARP expression in EWS cells, and sensitized these cells to ionizing radiation. These data provide support for ETS regulation of PARP expression levels, and implicate ETS transcription factors in the radiation response of EWS cells.

show abstract

Section: Inhibition Of Ets1 Expression Enhances Growth Retardation Ofmentioning

confidence: 82%

Regulation of the human poly(ADP-ribose) polymerase promoter by the ETS transcription factor

et al. 1999

View full text Add to dashboard Cite

show abstract

“…EWS/ETS aberrant transcription factors could activate the hCRD-BP/IMP-1 gene via the 2 ETS-2 binding sites in the promoter region and the additional one downstream of the transcription-start site. 13 So far, we can only speculate about the biologic role of hCRD-BP/IMP-1 in sarcomas, but previous studies have indicated that these tumors exhibit altered expression of c-myc 14 and IGF-II, 15,16 both of which could promote tumor growth. For example, in osteosarcomas, several of which (6/8) expressed hCRD-BP, upregulated c-myc expression is frequently not associated with gene amplification.…”

Section: C-myc Mrna Levels In Crd-bp/imp-1-negative and -Positive Tummentioning

confidence: 99%

“…16 However, established cell lines containing the t(11;22) translocation of Ewing's or PNET origin do not express IGF-II mRNA. 15 Ectopic expression of hCRD-BP/IMP-1 may result in upregulation of c-myc expression, permitting increased proliferation rates. It is well established that c-myc overexpression alone, although not sufficient to transform cells, perturbs many aspects of cellular physiology that are altered in transformed cells, such as cell growth and metabolism, cell-cycle rate, apoptosis, adhesion and cytoskeletal organization.…”

Section: C-myc Mrna Levels In Crd-bp/imp-1-negative and -Positive Tummentioning

confidence: 99%

C‐MYC and IGF‐II mRNA‐binding protein (CRD‐BP/IMP‐1) in benign and malignant mesenchymal tumors

et al. 2001

View full text Add to dashboard Cite

Mouse coding region determinant-binding (mCRD-BP)and human IGF-II mRNA-binding 1 (hIMP-1) proteins are orthologous mRNA-binding proteins that recognize c-myc and IGF-II mRNA, respectively, and regulate their expression posttranscriptionally. Here, we confirm that human CRD-BP/IMP-1 binds to c-myc mRNA and that it is predominantly expressed in fetal tissues. Moreover, hCRD-BP/IMP-1 expression was detected in cell lines of neoplastic origin and in selected primary tumors. In a series of 33 malignant and 10 benign mesenchymal tumors, 73% and 40%, respectively, were found to express hCRD-BP/IMP-1. In particular, expression was significant in 14 Ewing's sarcomas, all of which were positive. The data suggest that hCRD-BP/IMP-1 plays a role in abnormal cell proliferation in mesenchymal tumors.

show abstract

“…Several potential autocrine growth factor loops have also been described. The presence of an intact insulin-like growth factor type I receptor (IGFRI) appears to be essential for transformation by EWS ± ETS proteins and this receptor may function in survival and/or mitogenic signaling in ET (Scotlandi et al, 1996;Toretsky et al, 1997;Yee et al, 1990). We have reported that the mammalian homologue of bombesin, gastrin releasing peptide (GRP), functions as an autocrine growth factor in these tumors (Lawlor et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Anchorage-independent multi-cellular spheroids as an in vitro model of growth signaling in Ewing tumors

et al. 2002

View full text Add to dashboard Cite

Little is known about the growth-signaling pathways that govern the proliferation of Ewing tumor (ET) cells either in vitro or in vivo. We have studied signal transduction pathways in ET cell lines and compared kinase expression levels and proliferation rates with primary tumors. Cell lines were studied both as conventional adherent monolayers and as anchorage-independent multi-cellular spheroids. Importantly, we observed signi®cant di erences between these in vitro models and found that ET spheroids were more closely related to primary tumors with respect to cell morphology, cell ± cell junctions, proliferative index and kinase activation. Monolayer ET cells demonstrated serum-dependent phosphorylation of ERK1/2 and AKT and constitutively high serum-independent cyclin D1 protein expression. However, when ET cells were placed in suspension culture, there was immediate serum-independent activation of ERK1/2 and AKT. In addition, cyclin D1 protein expression was completely blocked until stable multicellular spheroids had formed, indicating that cell ± cell adhesion is necessary for the proliferation of anchorage independent ET cells. This reduction in cyclin D1 expression was post-transcriptional and could be mimicked in monolayer cells by treatment with phosphatidyl inositol-3 kinase (PI3K) inhibitors. Moreover, PI3K inhibition signi®cantly reduced ET cell proliferation and, in primary ET samples, cyclin D1 expression correlated with expression of activated AKT. Thus, the PI3K ± AKT pathway appears to be critical for the proliferation of ET cells both in vitro and in vivo and tumor cell growth in vivo may be better represented by the study of anchorage-independent multi-cellular spheroids.

show abstract

Insulin-like growth factor I expression by tumors of neuroectodermal origin with the t(11;22) chromosomal translocation. A potential autocrine growth factor.

Cited by 157 publications

References 41 publications

Regulation of the human poly(ADP-ribose) polymerase promoter by the ETS transcription factor

Regulation of the human poly(ADP-ribose) polymerase promoter by the ETS transcription factor

C‐MYC and IGF‐II mRNA‐binding protein (CRD‐BP/IMP‐1) in benign and malignant mesenchymal tumors

Anchorage-independent multi-cellular spheroids as an in vitro model of growth signaling in Ewing tumors

Contact Info

Product

Resources

About