Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma

Thiele, Carol J.; Reynolds, C. Patrick; Israel, Mark A.

doi:10.1038/313404a0

Cited by 584 publications

(383 citation statements)

References 22 publications

Supporting

Mentioning

352

Contrasting

Unclassified

Order By: Relevance

“…MicroRNA-34a as a tumor suppressor in neuroblastoma C Welch et al overexpressing miR-34a, confirming that miR-34a targets E2F3 mRNA (Figure 4b) All trans-retinoic acid (ATRA) induces the terminal differentiation of NB cells (Thiele et al, 1985). To test whether miR-34a is induced during the differentiation process, we analysed the expression level of miR-34a in SK-N-BE cells treated with ATRA.…”

mentioning

confidence: 63%

MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells

2007

View full text Add to dashboard Cite

Neuroblastoma (NB) is one of the most common forms of cancer in children, accounting for 15% of pediatric cancer deaths. The clinical course of these tumors is highly variable and is dependent on such factors as age at presentation, stage, ploidy and genomic abnormalities. Hemizygous deletion of chromosome 1p occurs in approximately 30% of advanced stage tumors, is associated with a poor prognosis, and likely leads to the loss of one or more tumor suppressor genes. We show here that microRNA (miRNA)-34a (1p36.23) is generally expressed at lower levels in unfavorable primary NB tumors and cell lines relative to normal adrenal tissue and that reintroduction of this miRNA into three different NB cell lines causes a dramatic reduction in cell proliferation through the induction of a caspase-dependent apoptotic pathway. As a potential mechanistic explanation for this observation, we demonstrate that miR-34a directly targets the messenger ribonucleic acid (mRNA) encoding E2F3 and significantly reduces the levels of E2F3 protein, a potent transcriptional inducer of cell-cycle progression. Furthermore, miR-34a expression increases during retinoic acidinduced differentiation of the SK-N-BE cell line, whereas E2F3 protein levels decrease. Thus, adding to the increasing role of miRNAs in cancer, miR-34a may act as a suppressor of NB tumorgenesis.

show abstract

mentioning

confidence: 63%

MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells

2007

View full text Add to dashboard Cite

show abstract

“…During this di erentiation these cells withdraw permanently from the cell cycle (Thiele et al, 1985(Thiele et al, , 1988Abemayor and Sidell, 1989). We followed this e ect bȳ owcytometric analysis of S-phase content (Figures 1 and 2).…”

Section: Resultsmentioning

confidence: 99%

“…F9 di erentiation into cells resembling parietal endoderm was a ected by additional of retinoic acid (®nal concentration 0.3 mM) to the medium (Strickland and Mahdavi, 1978). Neuronal di erentiation of SK-N-SH cells and LAN-1 cells was performed by adding retinoic acid (®nal concentration 20 mM) or DMSO (®nal concentration 1.5%) into the medium (Thiele et al, 1985(Thiele et al, , 1988Abemayor and Sidell, 1989;Tahira et al, 1991;Kranenburg et al, 1995).…”

Section: Cells and Tissue Culturementioning

confidence: 99%

A role of the tuberous sclerosis gene-2 product during neuronal differentiation

et al. 1998

View full text Add to dashboard Cite

Tuberous sclerosis is an autosomal dominant disorder. Besides the development of benign growths (hamartomas) in di erent tissues, one hallmark of this disease is the presence of highly epileptogenic dysplastic lesions in the cerebral cortex (tubers) composed of abnormal shaped neurones. Patients often show evidence of severe mental retardation. Linkage analysis revealed two diseasedetermining genes on chromosome 9 and chromosome 16. The TSC2 gene on chromosome 16 encodes a 1784-amino acid putative tumour suppressor protein, tuberin, that functions as a GTPase-activating protein. Here we show that tuberin expression is upregulated upon induction of neuronal di erentiation in the neuroblastoma cell lines SK-N-SH and LAN-1. This upregulation occurs at post-transcriptional level and is independent of the proliferation status. TSC2 expression is una ected during di erentiation of C2C12 myoblasts into myotubes and of F9 embryonal carcinoma cells into cells resembling parietal endoderm. Antisense inhibition of tuberin expression in SK-N-SH or LAN-1 cells inhibits neuronal di erentiation, but does not a ect the di erentiation of F9 cells. Ectopic overexpression of TSC2 not only reverts the antisense-associated phenotype but furthermore accelerates the neuronal di erentiation process. Our data show for the ®rst time that tuberin plays a critical role in neuronal di erentiation. Such role is consistent with the phenotype of tuberous sclerosis patients, who inherit one defective TSC2 allele, and frequently lose the remaining normal allele in many of the tubers/hamartomas which develop in the central nervous system of these patients.

show abstract

“…Our results show that stimulation of PKC or Ras/MAPK which elicit an arrest in cell growth and promote maturation in these cells converges with the actions of retinoids to activate RARb gene transcription providing an example of cross talk among di erent signaling pathways. An inhibition of expression of N-myc in cells with this oncogene ampli®ed (Thiele et al, 1985), or the induction of TrkB, a tyrosine kinase receptor known to be important in neuron survival and di erentiation, may be some of the mechanisms by which RA subsequently causes neuroblastoma cell maturation (Kaplan et al, 1993;Nakagawara et al, 1994). Retinoids have proven to be of clinical use in the treatment of di erent tumors.…”

Section: Discussionmentioning

confidence: 99%

Differentiation of neuroblastoma cells by phorbol esters and insulin-like growth factor 1 is associated with induction of retinoic acid receptor β gene expression

Pérez-Juste

Aranda

1999

Oncogene

View full text Add to dashboard Cite

The retinoic acid (RA) receptor b isoform (RARb) plays an important role in RA-induced di erentiation of human neuroblastoma. In this study we show that insulin-like growth factor 1 (IGF-1) and tetradecanoyl phorbol acetate (TPA) induce RARb gene expression in neuroblastoma SH-SY5Y cells. IGF-1 and TPA caused a marked induction of RARb2 promoter activity and had a synergistic e ect with RA that also upregulates transcription. The e ect of RA is mediated by two RA responsive elements (RAREs), whereas the IGF-1 and TPA actions are independent of the RAREs and map to sequences that overlap the TATA box. These results suggest that the signaling pathways stimulated by TPA and IGF-1 could modify the components assembled at the core RARb2 promoter and activate transcription. Expression of Ras Val12 mimics the e ect of IGF-1 and TPA on the promoter, and a dominant negative Ras mutant abrogates activation. A dominant negative Raf also blocks activation showing that the Ras-Raf pathway mediates stimulation of the RARb2 promoter. Our results show that neuronal di erentiation induced by non-retinoid agents that activate Ras is accompanied by increased transcription of the RARb gene.

show abstract

Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma

Cited by 584 publications

References 22 publications

MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells

MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells

A role of the tuberous sclerosis gene-2 product during neuronal differentiation

Differentiation of neuroblastoma cells by phorbol esters and insulin-like growth factor 1 is associated with induction of retinoic acid receptor β gene expression

Contact Info

Product

Resources

About