TGFbeta can modulate neuroblastoma (NB) cell proliferation and differentiation in vitro. In this study we used a NB cell line (LAN-5) which has been shown to partially respond to TGFbeta and to present high levels of TGFbeta receptor type I and low levels of receptor type II (TbetaRII) on the cell surface. To evaluate the role of TbetaRII in mediating TGFbeta effects, LAN-5 cells were transfected with an expression vector containing the human full-length TbetaRII cDNA or with the empty vector pcDNA3. Compared to control CLV3 cells (transfected with empty plasmid) and parental LAN-5 cells, isolated neomycin-resistant clones (CL1 and CL3) expressed higher levels of TbetaRII, had reduced cell growth rate in vitro, and were unable to form tumors in vivo. Furthermore, isolated clones modified their morphology, assuming a terminally differentiated neuronal phenotype. Immunocytochemical staining demonstrated a basal increased expression of neural-specific markers, such as axonal growth-associated protein (GAP43) and neurofilaments (NF200). TGFbeta treatment further increased the synthesis of NF200 and GAP43 in the transfected clones as revealed by Western blot analysis. These data indicate that TbetaRII overexpression potentiates the TGFbeta signal transduction pathway, reverting NB cell neoplastic phenotype with the reduction of proliferation rate and the induction of terminal maturation.

Turco, A., Scarpa, S., Coppa, A., Baccheschi, G., Palumbo, C., Leonetti, C., et al. (2000). Increased TGFbeta type II receptor expression suppresses the malignant phenotype and induces differentiation of human neuroblastoma cells. EXPERIMENTAL CELL RESEARCH, 255(1), 77-85 [10.1006/excr.1999.4750].

Increased TGFbeta type II receptor expression suppresses the malignant phenotype and induces differentiation of human neuroblastoma cells

PALUMBO, CAMILLA;
2000-02-25

Abstract

TGFbeta can modulate neuroblastoma (NB) cell proliferation and differentiation in vitro. In this study we used a NB cell line (LAN-5) which has been shown to partially respond to TGFbeta and to present high levels of TGFbeta receptor type I and low levels of receptor type II (TbetaRII) on the cell surface. To evaluate the role of TbetaRII in mediating TGFbeta effects, LAN-5 cells were transfected with an expression vector containing the human full-length TbetaRII cDNA or with the empty vector pcDNA3. Compared to control CLV3 cells (transfected with empty plasmid) and parental LAN-5 cells, isolated neomycin-resistant clones (CL1 and CL3) expressed higher levels of TbetaRII, had reduced cell growth rate in vitro, and were unable to form tumors in vivo. Furthermore, isolated clones modified their morphology, assuming a terminally differentiated neuronal phenotype. Immunocytochemical staining demonstrated a basal increased expression of neural-specific markers, such as axonal growth-associated protein (GAP43) and neurofilaments (NF200). TGFbeta treatment further increased the synthesis of NF200 and GAP43 in the transfected clones as revealed by Western blot analysis. These data indicate that TbetaRII overexpression potentiates the TGFbeta signal transduction pathway, reverting NB cell neoplastic phenotype with the reduction of proliferation rate and the induction of terminal maturation.
25-feb-2000
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/04 - PATOLOGIA GENERALE
English
Con Impact Factor ISI
Animals; Humans; Gene Expression; Cell Differentiation; Mice; Mice, Nude; Protein-Serine-Threonine Kinases; Neuroblastoma; Phenotype; Tumor Cells, Cultured; Transfection; Genes, Reporter; Receptors, Transforming Growth Factor beta; Male
Turco, A., Scarpa, S., Coppa, A., Baccheschi, G., Palumbo, C., Leonetti, C., et al. (2000). Increased TGFbeta type II receptor expression suppresses the malignant phenotype and induces differentiation of human neuroblastoma cells. EXPERIMENTAL CELL RESEARCH, 255(1), 77-85 [10.1006/excr.1999.4750].
Turco, A; Scarpa, S; Coppa, A; Baccheschi, G; Palumbo, C; Leonetti, C; Zupi, G; Colletta, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/89449
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