Induction of RET Proto-Oncogene Expression in Neuroblastoma Cells Precedes Neuronal Differentiation and Is Not Mediated by Protein Synthesis

Bunone, Giuseppe; Borrello, M. G.; Picetti, Roberto; Bongarzone, Italia; Peverali, Fiorenzo A.; Franciscis, Vittorio de; Valle, Giuliano Della; Pierotti, Marco A.

doi:10.1006/excr.1995.1067

Cited by 50 publications

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“…In neural crest-derived cells, RET is predicted to function in both differentiation and proliferation processes. Activated forms of RET have the ability to induce di erentiation in PC12 cells (Bunone et al, 1995;Asai et al, 1995;Califano et al, 1995). In contrast, activated RET is transforming in NIH3T3 cells, resulting in proliferation Califano et al, 1995;Santoro et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

The expression of RET and its multiple splice forms in developing human kidney

et al. 1997

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A series of inductive events between two di erent cell groups, the ureteric bud epithelium and metanephric mesenchyme, gives rise to the functional mammalian kidney. These reciprocal inductive interactions involve a number of molecules, one of which is the RET receptor tyrosine kinase. The phenotype of mice lacking functional RET includes kidney agenesis or severe dysgenesis, indicating a requirement for RET in kidney organogenesis. To investigate RET expression in human kidney development, we used a semi-quantitative RT ± PCR-based strategy to examine a panel of kidney RNA samples ranging from 8 ± 24 weeks gestational age. We found RET expression was highest earlier in development (14 weeks) with expression decreasing through to 24 weeks gestation. While three alternative RET transcripts generated by exon skipping at the 5' end of the gene were all detected throughout kidney development, expression of one transcript, RET2/6, where exon 2 was spliced to exon 6, varied relative to full length RET during this period. Levels of RET2/6 were highest at the earliest age of fetal kidney examined (8 weeks) and decreased relative to all other RET transcripts to low adult levels. The period of high expression coincides with a period of rapid bud bifurcation. Thus, it is possible that RET2/6 has a role in the early growth and di erentiation of the human kidney.

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Section: Discussionmentioning

confidence: 99%

The expression of RET and its multiple splice forms in developing human kidney

et al. 1997

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“…The human NB cell line SK-N-BE (Biedler et al, 1973) was grown in RPMI-1640 medium supplemented with 2 mM glutamine, 15% FCS and gentamycin (50 mg/ml), at 378C in a humidi®ed atmosphere with 5% CO 2 , as previously described (Bunone et al, 1995). Hygromycin resistant clones were grown in complete medium plus 300 mg/ml hygromycin.…”

Section: Cell Culturementioning

confidence: 99%

“…RNA samples (20 mg each) were fractionated by 1% agarose/2.2 M formaldehyde gel electrophoresis, blotted onto nitrocellulose ®lters (Amersham) and hybridized with 32 P-labeled DNA probes, as previously described (Bunone et al, 1995). The following cDNA fragments were used as probes: (a) the 1.5 kb ApaI ± EcoRI fragment of p75 NTR cDNA; (b) the 1.2 kb BamHI ± EcoRI fragment of TrkA cDNA puri®ed from the pDM17 plasmid, which recognizes the tyrosine kinase domain (Martin-Zanca et al, 1989).…”

Section: Rna Isolation and Northern Blot Analysismentioning

confidence: 99%

Induction of apoptosis by p75 neurotrophin receptor in human neuroblastoma cells

et al. 1997

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The low-a nity nerve growth factor receptor p75 NTR belongs to a membrane receptor superfamily whose members, in certain cell types, are able to transduce an apoptotic signal. To investigate the e ect of p75 NTR expression in neuroblastoma cells, we transfected the p75 NTR cDNA into SK-N-BE cells, a neuroblastoma cell line that lacks expression of both p75 NTR and TrkA. Cell clones expressing elevated levels of p75 NTR showed a high degree of cell death by apoptosis, even in serumsupplemented medium. Moreover, the level of apoptosis correlated directly with the expression level of the receptor, indicating that p75 NTR could activate the cell death program by itself. Clones expressing p75 NTR showed a dramatic increase of cell death when switched into serum-free medium; these cultures rapidly extinguished. This apoptotic e ect was greatly inhibited by NGF treatment. Our results support the hypothesis that p75 NTR , when it is not bound by NGF, may play a role in neuronal selection during embryonic development and suggest that neuroblastomas may arise from immature neuroblasts that escape programmed cell death. Therefore, the loss of p75 NTR expression in developing neural crest cells might be a primary event in the genesis of neuroblastoma.

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“…Treatment of several human neuroblastoma cell lines with RA rapidly induces Ret expression by several times. Increased Ret expression is an early event followed by the expression of a differentiated phenotype, which includes expression of growthassociated protein-43 (GAP-43), nerve growth factor-inducible protein (VGF), neurite outgrowth, and inhibition of cell proliferation (12,14,15).…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we sought to better understand how activation of Ret participates to the differentiation of human neuroblastoma cells. To minimize the contribution of TrkB, here, we chose to use the human SK-N-BE(2) neuroblastoma cell line (hereafter named SK-N-BE), in which RA-induced differentiation is preceded by a rapid accumulation of Ret but not of Trk family receptors that are not or poorly expressed (14,16). We used two specific interfering molecules to inhibit Ret function: the EC-Ret peptide that blocks Ret stimulation by competing for binding to the ligandGFRa complex (17,18) and the D4 aptamer that inhibits Ret activity by directly binding the receptor (19).…”

Section: Introductionmentioning

confidence: 99%